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1.
Medicine (Baltimore) ; 103(20): e35050, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758863

RESUMEN

BACKGROUND: To investigate the regulatory patterns of Chinese patent medicine (CPM) interventions on lipid metabolism disorders in patients with type 2 diabetes mellitus (T2DM) complicated by ischemic stroke. METHODS: Two researchers independently searched 8 major databases and created a comprehensive database containing all randomized controlled trials (RCTs) that investigated the application of "blood-activating and stasis-removing" CPM in the treatment of stroke combined with T2DM until October 1, 2022. The collected data were compiled and organized in Excel. Quality assessment was performed using the Cochrane 5.3 bias risk assessment tool, and the network meta-analysis was conducted using R software. RESULTS: A total of 12 articles were included in the final analysis, covering 4 types of CPM: Naoxintong Capsules (NXT), Tongmai Jiangtang Capsules, Tongxinluo Capsules (TXL), and Yindan Xinnaotong Soft Capsules. Among these, CPM formulations containing herbs with blood-activating and stasis-removing properties were the most commonly used. The results of the network meta-analysis are as follows: (1) the combination of 3 CPM formulations showed superior efficacy in improving total cholesterol levels compared to conventional Western medicine treatment (CT). In particular, Yindan Xinnaotong Soft Capsules + CT (surface under the cumulative ranking curve [SUCRA] = 97.24%) demonstrated the highest efficacy, followed by NXT + CT (SUCRA = 66.23%), and then TXL + CT (SUCRA = 55.16%). (2) TXL + CT treatment exhibited the most promising efficacy in improving triglyceride levels (P < .05), while the effects of the other 3 CPM formulations were not statistically significant. (3) In terms of improving low-density lipoprotein levels, NXT + CT (SUCRA = 82.27%) showed better efficacy than TXL + CT (SUCRA = 73.99%), while the effects of the other 2 CPM formulations were not statistically significant. (4) The combination of CPM formulations and CT resulted in a lower incidence of adverse reactions compared to CT (P < .05). CONCLUSION: The treatment of patients with T2DM complicated by ischemic stroke commonly involved the use of "blood-activating and stasis-removing" herbal medicines. These herbal medicines have shown effectiveness in regulating patients' blood lipid levels. However, it is crucial to acknowledge that the analysis was influenced by variations in the number and quality of RCTs involving different CPM formulations. Therefore, additional validation through large-scale, high-quality RCT studies is required.


Asunto(s)
Diabetes Mellitus Tipo 2 , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Metaanálisis en Red , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Tradicional China/métodos
2.
Int J Biol Macromol ; 271(Pt 2): 132584, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38795881

RESUMEN

This study evaluated the regulatory effects of Astragalus membranaceus polysaccharides (AMP) on lipid metabolism disorders induced by a high-fat diet (HFD) in spotted sea bass (Lateolabrax maculatus). Compared with the normal diets (10 % lipids), diets containing 15 % lipid levels were used as the high-fat diet (HFD). Three levels of the AMP (0.06 %, 0.08 %, 0.10 %) were added in the HFD and used as experimental diets. A total of 375 spotted sea bass (average weight 3.00 ± 0.01 g) were divided into 15 tanks and deemed as 5 groups, with each tank containing 25 fish. Fish in each group were fed with different diets for 56 days. After feeding, the HFD induced lipid metabolism disorders in fish, as evidenced by elevated serum lipids, malonaldehyde levels, and more severe liver damage. The AMP alleviated the HFD-induced liver damage, as evidenced by the reduced severity of liver histological lesions and malonaldehyde levels. The low-density lipoprotein cholesterol was reduced, and the expression of FAS and PPAR-α were down and up-regulated, respectively. However, the AMP had a limited ability to affect the serum lipids and abdominal fat percentage. These results reveal the potential of the AMP used in aquaculture to regulate lipid metabolism disorders induced by the HFD.


Asunto(s)
Astragalus propinquus , Lubina , Dieta Alta en Grasa , Metabolismo de los Lípidos , Polisacáridos , Animales , Dieta Alta en Grasa/efectos adversos , Polisacáridos/farmacología , Astragalus propinquus/química , Metabolismo de los Lípidos/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/etiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , PPAR alfa/metabolismo , Lípidos/sangre
3.
J Nutr ; 152(4): 939-949, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-36967184

RESUMEN

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Trastornos del Metabolismo de los Lípidos , Ratones , Masculino , Animales , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , LDL-Colesterol , Sulfatos/uso terapéutico , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Peso Corporal , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/etiología
4.
J Nutr ; 152(4): 939-949, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34958377

RESUMEN

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.


Asunto(s)
Dieta Alta en Grasa , Trastornos del Metabolismo de los Lípidos , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Polisacáridos/farmacología , Sulfatos/uso terapéutico
5.
Biomed Res Int ; 2021: 9942152, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34485530

RESUMEN

Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), liver X receptors (LXR), ATP-binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real-time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC-1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC-1α/LXR pathway. Of note, silencing PGC-1α reversed the promotive effect of MOR on PA- or HG-induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC-1α.


Asunto(s)
Glucosa/administración & dosificación , Glicósidos/farmacología , Enfermedades Renales/metabolismo , Túbulos Renales/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Ácido Palmítico/farmacología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Animales , Línea Celular , Inhibidores Enzimáticos/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/patología , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/patología , Ratones , Extractos Vegetales/farmacología , Transducción de Señal , Edulcorantes/farmacología
6.
Appl Physiol Nutr Metab ; 46(11): 1322-1330, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34038646

RESUMEN

SESN2 and JNK are emerging powerful stress-inducible proteins in regulating lipid metabolism. The aim of this study was to determine the underlying mechanism of SESN2/JNK signaling in exercise to improve lipid disorder induced by high-fat diet (HFD). Our data showed that HFD and SESN2 knockout resulted in abnormalities including elevated body weight, increased fat mass, serum total cholesterol, lipid biosynthesis related proteins, and a concomitant increase of pJNK-Thr183/Tyr185. The above changes were reversed by exercise training. SESN2 silencing or JNK inhibition in palmitate-treated C2C12 further confirmed that SESN2 and JNK play a vital role in lipid biosynthesis. Rescue experiment further demonstrated that SESN2 reduced lipid biosynthesis through inhibition of JNK. SESN2/JNK signaling axis regulates lipid biosynthesis in both animal and cell models with abnormalities of lipid metabolism induced by HFD or palmitate treatment. This study provided evidence that exercise ameliorated lipid metabolic disorder induced by HFD feeding or by SESN2 knockout. SESN2 may improve lipid metabolism through inhibition JNK expression in skeletal muscle cells, providing a molecular mechanism that may represent an attractive target for the treatment of lipid disorder. Novelty: Exercise improved lipid disorder induced by HFD feeding and SESN2 knockout. SESN2 and JNK play a vital role in lipid biosynthesis in vivo and in vitro. SESN2 suppressed JNK to improve lipid metabolism in skeletal muscle cells.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/prevención & control , Peroxidasas/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Composición Corporal , Línea Celular , Trastornos del Metabolismo de los Lípidos/etiología , Lípidos/biosíntesis , Lípidos/sangre , Hígado/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Animales , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/metabolismo
7.
Pediatr Ann ; 50(3): e105-e112, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34038650

RESUMEN

Current scientific evidence has proven that atherosclerosis is a process that begins in childhood and tracks into adulthood, likely culminating in adverse cardiovascular events such as coronary artery disease, peripheral artery disease, and stroke. In addition, the obesity epidemic and increasing awareness of genetic lipid disorders has made the understanding and management of lipid disorders necessary for pediatricians. Childhood offers a unique opportunity for preventing, modifying, or eliminating risk factors and, in doing so, reversing or slowing the process of atherosclerosis. In general, management involves targeted lifestyle interventions such as strict dietary changes and increases in physical activity. In some circumstances, pharmacotherapy, even in childhood, is warranted. [Pediatr Ann. 2021;50(3):e105-e112.].


Asunto(s)
Aterosclerosis/prevención & control , Estilo de Vida , Trastornos del Metabolismo de los Lípidos , Obesidad , Niño , Dieta , Ejercicio Físico , Humanos , Trastornos del Metabolismo de los Lípidos/diagnóstico , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/terapia , Tamizaje Masivo , Síndrome Metabólico , Pediatría , Factores de Riesgo
8.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33926097

RESUMEN

Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Trastornos del Metabolismo de los Lípidos/etiología , Metabolismo de los Lípidos/fisiología , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Sistema Enzimático del Citocromo P-450/fisiología , Dieta Alta en Grasa , Dislipidemias/metabolismo , Hígado Graso/metabolismo , Femenino , Glucosa/metabolismo , Insulina/metabolismo , Resistencia a la Insulina , Grasa Intraabdominal/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/fisiopatología , Lípidos/sangre , Lipogénesis/efectos de los fármacos , Lipólisis , Hígado/metabolismo , Menopausia/metabolismo , Menopausia/fisiología , Obesidad/metabolismo , Ovariectomía/efectos adversos , Posmenopausia/metabolismo , Posmenopausia/fisiología , Ratas , Ratas Wistar , Triglicéridos/metabolismo , Aumento de Peso
9.
Food Funct ; 11(11): 10033-10046, 2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-33135040

RESUMEN

Luteolin (LU) is a flavonoid compound and metformin hydrochloride (MH) is a kind of drug. Studies have shown that both LU and MH have the function of hypoglycemic effect. However, there are few reports indicating that LU cooperated with MH (LU·MH) can relieve lipid metabolism disorders and optimize intestinal flora compositions of high-fat diet mice. In this research, we investigated the effects of LU, MH and LU·MH on lipid metabolism disorders and intestinal flora composition in high-fat diet mice. The study found that compared with high-fat diet (HFD) alone, LU, MH and LU·MH could significantly reduce the lipid metabolism disorder. Furthermore, compared with LU or MH alone, the biochemical indicators of LU·MH were significantly improved and the results of the histopathological section also showed that LU·MH has stronger liver repair ability. It revealed that the potential mechanisms of the LU·MH alleviating lipid metabolism disorders were involved in the simultaneous regulation of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1. In addition, LU·MH could regulate the intestinal flora compositions. This includes significantly reducing the ratio of Firmicutes and Bacteroidetes(F/B) and at the family level, increasing the relative abundance of Lachnospiraceae, Helicobacteraceae, Marinifilaceae and Peptococcaceae to relieve lipid metabolism disorders. In conclusion, the work found that LU·MH regulates the signal pathway of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1 simultaneously and decreases the ratio of F/B, as well as increases the relative abundance of certain microbiota to alleviate the lipid metabolism disorders of HFD-fed mice.


Asunto(s)
Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Luteolina/administración & dosificación , Metformina/administración & dosificación , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Dieta Alta en Grasa/efectos adversos , Quimioterapia Combinada , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/microbiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo
10.
Nutrients ; 12(10)2020 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-33080795

RESUMEN

Blood levels of iron and copper, even within their normal ranges, have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. This study aims to examine the causal clinical effects of blood iron and copper with Mendelian randomization (MR) analyses. Genetic instruments for the blood levels of iron and copper were curated from existing genome-wide association studies. Candidate clinical outcomes were identified based on a phenome-wide association study (PheWAS) between these genetic instruments and a wide range of phenotypes in 310,999 unrelated individuals of European ancestry from the UK Biobank. All signals passing stringent correction for multiple testing were followed by MR analyses, with replication in independent data sources where possible. We found that genetically predicted higher blood levels of iron and copper are both associated with lower risks of iron deficiency anemia (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.67-0.85, p = 1.90 × 10-6 for iron; OR = 0.88, 95% CI: 0.78-0.98, p = 0.032 for copper), lipid metabolism disorders, and its two subcategories, hyperlipidemia (OR = 0.90, 95% CI: 0.85-0.96, p = 6.44 × 10-4; OR = 0.92, 95% CI: 0.87-0.98, p = 5.51 × 10-3) and hypercholesterolemia (OR = 0.90, 95% CI: 0.84-0.95, p = 5.34 × 10-4; OR = 0.93, 95% CI: 0.89-0.99, p = 0.022). Consistently, they are also associated with lower blood levels of total cholesterol and low-density lipoprotein cholesterol. Multiple sensitivity tests were applied to assess the presence of pleiotropy and the robustness of causal estimates. Regardless of the approaches, consistent evidence was obtained. Moreover, the unique clinical effects of each blood mineral were identified. Notably, genetically predicated higher blood iron is associated with an enhanced risk of varicose veins (OR = 1.28, 95% CI: 1.15-1.42, p = 4.34 × 10-6), while blood copper is positively associated with the risk of osteoarthrosis (OR = 1.07, 95% CI: 1.02-1.13, p = 0.010). Sex-stratified MR analysis further revealed some degree of sex differences in their clinical effects. Our comparative PheWAS-MR study of iron and copper comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in hyperlipidemia and hypercholesterolemia. Given the modifiable nature of blood mineral status and the potential for clinical intervention, these findings warrant further investigation.


Asunto(s)
Cobre/sangre , Estudio de Asociación del Genoma Completo , Hierro/sangre , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/genética , Análisis de la Aleatorización Mendeliana , Fenotipo , Anemia Ferropénica , Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Metabolismo de los Lípidos , Trastornos del Metabolismo de los Lípidos/metabolismo , Masculino , Osteoartritis/etiología , Polimorfismo de Nucleótido Simple , Riesgo , Caracteres Sexuales , Reino Unido , Várices/etiología , Población Blanca
11.
Endocrinology ; 161(9)2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32790834

RESUMEN

Inflammasomes are multiprotein complexes that respond to pathogen or host associated damage markers, leading to caspase-1 maturation and processing of pro-inflammatory cytokines. Initially, inflammasomes were implicated primarily in inflammatory and infectious conditions. However, increasing evidence demonstrates broader roles beyond inflammation, including regulation of adipose tissue metabolism after burns. Here, we conducted a search for articles on PubMed, Web of Science, Embase, Scopus, and UpToDate with applied search strategies including a combination of "burns," "trauma," "(NLRP3) inflammasome," "metabolic conditions," "white adipose tissue," "macrophages," "browning," and "lipolysis" and included papers from 2000 to 2020. We discuss unexpected roles for NLRP3, the most characterized inflammasome to date, as a key metabolic driver in a variety of conditions. In particular, we highlight the function of NLRP3 inflammasome in burn trauma, which is characterized by both hyperinflammation and hypermetabolism. We identify a critical part for NLRP3 activation in macrophage dynamics and delineate a novel role in postburn white adipose tissue remodeling, a pathological response associated with hypermetabolism and poor clinical outcomes. Mechanistically, how inflammation and inflammasome activation is linked to postburn hypermetabolism is a novel concept to contemplate, and herein we provide evidence of an immunometabolic crosstalk between adipocytes and infiltrating macrophages.


Asunto(s)
Quemaduras/complicaciones , Inflamasomas/fisiología , Inflamación/etiología , Trastornos del Metabolismo de los Lípidos/etiología , Metabolismo/fisiología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Tejido Adiposo/fisiopatología , Animales , Quemaduras/metabolismo , Humanos , Inflamasomas/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Trastornos del Metabolismo de los Lípidos/inmunología , Trastornos del Metabolismo de los Lípidos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo
12.
J Clin Endocrinol Metab ; 105(9)2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32761088

RESUMEN

CONTEXT: Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. OBJECTIVE: To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. DESIGN: Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). SETTING: University hospital setting in The Netherlands. PATIENTS: Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. MAIN OUTCOME MEASURES: HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). RESULTS: During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P < 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P < 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. CONCLUSION: During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.


Asunto(s)
HDL-Colesterol/metabolismo , Hipotiroidismo/metabolismo , Trastornos del Metabolismo de los Lípidos/metabolismo , Adulto , HDL-Colesterol/sangre , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/patología , Trastornos del Metabolismo de los Lípidos/sangre , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/etiología , Masculino , Persona de Mediana Edad , Países Bajos , Sistema de Registros , Índice de Severidad de la Enfermedad , Hormonas Tiroideas/uso terapéutico , Tirotropina/sangre , Factores de Tiempo , Resultado del Tratamiento
13.
FASEB J ; 34(5): 6508-6520, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32232897

RESUMEN

This study aimed to evaluate the oxidative status and antioxidant capacity in maternal and fetal livers upon undernutrition as well as the connection between oxidative stress and lipid metabolism disorder. Ten ewes, who were pregnant for 115 days, were restricted to a 30% level of ad libitum feed intake to develop an undernourished model, while another 10 pregnant ewes were fed normally as controls. Undernutrition induced severe lipid metabolism disorder and oxidative stress in blood, maternal liver, and fetal liver. RNA-sequencing data displayed that antioxidant capacity was changed and antioxidant genes were downregulated in maternal and fetal livers of the undernourished model. Non-esterified fatty acids (NEFAs) and beta-hydroxybutyrate (BHBA) levels showed a positive correlation with oxidative indices and negative correlation with the expression of antioxidant genes both in maternal and fetal livers. Primary hepatocytes experiments confirmed that both high levels of NEFAs and BHBA could elicit oxidative stress and decrease antioxidant capacity, and the peroxisome proliferator-activated receptor alpha (PPARA)/retinoid X receptor alpha (RXRA) signaling pathway played a vital role in enhancing antioxidant capacity and relieving oxidative stress. In conclusion, maternal undernutrition induced lipid metabolism disorder, which downregulated antioxidant genes, decreased antioxidant activity, and further triggered oxidative stress both in maternal and fetal livers. Activation of PPARA/RXRA signaling could enhance antioxidant capacity and mitigate oxidative stress. Our findings contribute to protecting the pregnant mother and her fetus from oxidative stress.


Asunto(s)
Antioxidantes/metabolismo , Feto/patología , Trastornos del Metabolismo de los Lípidos/patología , Hígado/patología , Desnutrición/complicaciones , Estrés Oxidativo , Complicaciones del Embarazo/patología , Ácido 3-Hidroxibutírico/metabolismo , Animales , Ácidos Grasos no Esterificados/metabolismo , Femenino , Feto/metabolismo , Hepatocitos/metabolismo , Hepatocitos/patología , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Hígado/metabolismo , Intercambio Materno-Fetal , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/metabolismo , Ovinos , Transducción de Señal
14.
Endocr J ; 67(6): 593-605, 2020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32161203

RESUMEN

Thyroid hormone is crucial for regulating lipid and glucose metabolism, which plays essential role in maintaining the health of pregnant women and their offspring. However, the current literature is just focusing on the development of offspring born to the untreated mothers with hypothyroidism, rather than mothers themselves. Additionally, the interaction between hypothyroidism and pregnancy, and its impact on the women's health are still elusive. Therefore, this study was designed to compare the metabolic differences in dams with hypothyroidism starting before pregnancy and after pregnancy. Pre-pregnant hypothyroidism was generated in 5-week-old female C57/BL/6J mice using iodine-deficient diet containing 0.15% propylthiouracil for 4 weeks, and the hypothyroidism was maintained until delivery. Gestational hypothyroidism was induced in dams after mating, using the same diet intervention until delivery. Compared with normal control, gestational hypothyroidism exhibited more prominent increase than pre-pregnant hypothyroidism in plasma total cholesterol and low-density lipoprotein cholesterol, and caused hepatic triglycerides accumulation. Similarly, more significant elevations of protein expressions of SREBP1c and p-ACL, while more dramatic inhibition of CPT1A and LDL-R levels were also observed in murine livers with gestational hypothyroidism than those with pre-pregnant hypothyroidism. Moreover, the murine hepatic levels of total cholesterol and gluconeogenesis were dramatically and equally enhanced in two hypothyroid groups, while plasma triglycerides and protein expressions of p-AKT, p-FoxO1 and APOC3 were reduced substantially in two hypothyroid groups. Taken together, our current study illuminated that gestational hypothyroidism may elicit more pronounced lipid dysregulation in dams than dose the pre-pregnant hypothyroidism.


Asunto(s)
Hipotiroidismo/metabolismo , Trastornos del Metabolismo de los Lípidos/etiología , Metabolismo de los Lípidos , Complicaciones del Embarazo/metabolismo , Animales , Femenino , Fertilización/fisiología , Ganancia de Peso Gestacional/fisiología , Hiperglucemia/etiología , Hiperglucemia/metabolismo , Hiperglucemia/patología , Hipotiroidismo/complicaciones , Hipotiroidismo/patología , Hipotiroidismo/fisiopatología , Metabolismo de los Lípidos/fisiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/patología , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Páncreas/metabolismo , Páncreas/patología , Embarazo , Complicaciones del Embarazo/patología , Complicaciones del Embarazo/fisiopatología , Trastornos Puerperales/etiología , Trastornos Puerperales/metabolismo , Trastornos Puerperales/patología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Glándula Tiroides/fisiopatología , Factores de Tiempo
15.
FASEB J ; 34(5): 6198-6214, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32162746

RESUMEN

Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA-LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA-LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA-LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28-week-old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA-LPE alleviated mitochondria-dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A2 (cPLA2 ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria-mediated oxidative stress and apoptosis. UDCA-LPE inhibited the interaction between cPLA2 and mitochondria and reduced phospholipid hydrolysis-mediated injury. UDCA-LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.


Asunto(s)
Trastornos del Metabolismo de los Lípidos/prevención & control , Hepatopatías/prevención & control , Lisofosfolípidos/farmacología , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfolípidos/metabolismo , Daño por Reperfusión/complicaciones , Ácido Ursodesoxicólico/análogos & derivados , Animales , Apoptosis , Células Hep G2 , Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Hepatopatías/etiología , Hepatopatías/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/patología , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno , Ácido Ursodesoxicólico/farmacología
16.
Curr Diab Rep ; 19(12): 144, 2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31754839

RESUMEN

PURPOSE OF REVIEW: The goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression. RECENT FINDINGS: Mitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD. ABCA1 deficiency in podocytes leads to mitochondrial dysfunction observed with alterations of mitochondrial lipids, in particular, cardiolipin (a mitochondrial-specific phospholipid). However, through pharmacological reduction of cardiolipin peroxidation DKD progression is reverted. Lipid metabolism is significantly altered in the diabetic kidney and renders cellular components, such as the podocyte, susceptible to injury leading to worsened DKD progression. Dysfunction of the lipid metabolism pathway can also lead to mitochondrial dysfunction and mitochondrial lipid alteration. Future research aimed at targeting mitochondrial lipids content and function could prove to be beneficial for the treatment of DKD.


Asunto(s)
Nefropatías Diabéticas/fisiopatología , Glomérulos Renales/fisiopatología , Trastornos del Metabolismo de los Lípidos/fisiopatología , Metabolismo de los Lípidos/fisiología , Mitocondrias/fisiología , Receptor Cross-Talk/fisiología , Nefropatías Diabéticas/etiología , Humanos , Glomérulos Renales/patología , Trastornos del Metabolismo de los Lípidos/etiología , Lípidos/fisiología , Podocitos/fisiología
17.
Lipids Health Dis ; 18(1): 151, 2019 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31286991

RESUMEN

BACKGROUND: Free fatty acid (FFA) accumulation in proximal tubules plays a fundamental role in the progress of kidney disease. Here, we reported a rare case with undetectable serum FFAs and further evaluated the changes of serum FFAs in patients with chronic renal failure (CRF). METHODS: We analyzed the clinical data of a rare case and 574 CRF patients. The mRNA expression of lipoprotein lipase (LPL), hepatic lipase (HL) and fatty acid synthase (FASN) were determined in the rare case and 30 age-matched healthy males with qPCR. RESULTS: This rare case had serious proteinuria, hyperglycemia, lipid disorders and bilateral renal glomerular filtration dysfunction. Compared with healthy males, this case showed a 1.49-fold increase of LPL expression (P < 0.01), a 3.38-fold reduction of HL expression (P < 0.001), and no significant change of FASN expression (P > 0.05). In total, 21.6% of CRF patients showed abnormal FFAs. Biochemical parameters such as blood urea nitrogen (BUN) and creatinine (CREA) significantly differed among groups with low-, normal- or high-level-FFAs. Moreover, serum FFAs was found to be associated with BUN. FFAs decreased in the group with higher BUN (> 17.4 mmol/L) and in the group with lower estimated glomerular filtration rate (eGFR) (< 15 mL/min/1.73m2). CONCLUSIONS: The proteinuria, HL low expression and renal function failure may contribute to the FFA reduction, which might imply that the renal function is severely damaged.


Asunto(s)
Ácidos Grasos no Esterificados/sangre , Fallo Renal Crónico/sangre , Adulto , Anciano , Análisis Químico de la Sangre , Estudios de Casos y Controles , Acido Graso Sintasa Tipo I/genética , Femenino , Expresión Génica , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/fisiopatología , Lipasa/genética , Trastornos del Metabolismo de los Lípidos/sangre , Trastornos del Metabolismo de los Lípidos/etiología , Lipoproteína Lipasa/genética , Masculino , Persona de Mediana Edad , Proteinuria/sangre , Proteinuria/etiología
18.
Hum Mol Genet ; 28(R1): R49-R54, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31227825

RESUMEN

The prevalence of lipid disorders is alarmingly increasing in the Western world. They are the result of either primary causes, such as unhealthy lifestyle choices or inherited risk factors, or secondary causes like other diseases or medication. Atypical changes in the synthesis, processing and catabolism of lipoprotein particles may lead to severe hypercholesterolemia, hypertriglyceridemia or elevated Lp(a). Although cholesterol-lowering drugs are the most prescribed medications, not all patients achieve guideline recommended cholesterol levels with the current treatment options, emphasising the need for new therapies. Also, some lipid disorders do not have any treatment options but rely only on stringent dietary restriction. Patients with untreated lipid disorders carry a severe risk of cardiovascular disease, diabetes, non-alcoholic fatty liver disease and pancreatitis among others. To achieve better treatment outcome, novel selective gene expression and epigenetic targeting therapies are constantly being developed. Therapeutic innovations employing targeted RNA technology utilise small interfering RNAs, antisense oligonucleotides, long non-coding RNAs and microRNAs to regulate target protein production whereas viral gene therapy provides functional therapeutic genes and CRISPR/Cas technology relies on gene editing and transcriptional regulation. In this review, we will discuss the latest advances in clinical trials for novel lipid-lowering therapies and potential new targets in pre-clinical phase.


Asunto(s)
Trastornos del Metabolismo de los Lípidos/terapia , Animales , Ensayos Clínicos como Asunto , Terapia Combinada , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Evaluación Preclínica de Medicamentos , Terapia Genética/métodos , Vectores Genéticos/genética , Humanos , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Resultado del Tratamiento
19.
Nutrients ; 11(5)2019 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-31052523

RESUMEN

Free sugars overconsumption is associated with an increased prevalence of risk factors for metabolic diseases such as the alteration of the blood lipid levels. Natural fruit juices have a free sugar composition quite similar to that of sugar-sweetened beverages. Thus, could fruit juice consumption lead to the same adverse effects on health as sweetened beverages? We attempted to answer this question by reviewing the available evidence on the health effects of both sugar-sweetened beverages and natural fruit juices. We determined that, despite the similarity of fruits juices to sugar-sweetened beverages in terms of free sugars content, it remains unclear whether they lead to the same metabolic consequences if consumed in equal dose. Important discrepancies between studies, such as type of fruit juice, dose, duration, study design, and measured outcomes, make it impossible to provide evidence-based public recommendations as to whether the consumption of fruit juices alters the blood lipid profile. More randomized controlled trials comparing the metabolic effects of fruit juice and sugar-sweetened beverage consumption are needed to shape accurate public health guidelines on the variety and quantity of free sugars in our diet that would help to prevent the development of obesity and related health problems.


Asunto(s)
Bebidas/análisis , Jugos de Frutas y Vegetales/análisis , Edulcorantes/análisis , Adolescente , Adulto , Anciano , Sacarosa en la Dieta/efectos adversos , Femenino , Fructosa/metabolismo , Glucosa/metabolismo , Trastornos del Metabolismo de la Glucosa/etiología , Jarabe de Maíz Alto en Fructosa/efectos adversos , Humanos , Trastornos del Metabolismo de los Lípidos/etiología , Masculino , Persona de Mediana Edad , Nutrientes , Factores de Riesgo , Adulto Joven
20.
J Diabetes ; 11(2): 148-160, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30058212

RESUMEN

BACKGROUND: The prevalence of obesity is increasing rapidly worldwide, and dietary intake is strongly associated with obesity-related chronic diseases. However, key metabolic perturbations in obese young men with hyperlipidemia after high-fat diet (HFD) intervention are not yet clear, and remain to be determined. The aim of this study was to investigate the effects of a short-term HFD on glycolipid metabolism, insulin resistance (IR), and urinary metabolomic profiling in young obese men with hyperlipidemia. METHODS: Sixty young men (19-25 years; 30 normal weight, 30 obese with hyperlipidemia) were enrolled in the study. Differences in metabolomic profiling of urine between normal-weight and obese young men before and after 3 days intake of the HFD were investigated using ultra-HPLC-quadrupole time-of-flight mass spectrometry. RESULTS: After the HFD intervention, total cholesterol (TC), low-density lipoprotein cholesterol, fasting plasma glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly increased and high-density lipoprotein cholesterol was significantly decreased in obese men, but only TC was significantly increased in normal-weight subjects. Based on metabolic differences, normal-weight and obese men, and obese men before and after the HFD intervention could be separated into distinct clusters. Seventeen major metabolites were identified that were associated with type 2 diabetes mellitus, glycolipid metabolism and IR; the changes in these metabolites suggest metabolic changes in young obese males after short-term HFD intake. CONCLUSIONS: The findings of this study may contribute to increased understanding of the early biological adaptations of obesity with hyperlipidemia to HFD for the early prevention and control of diabetes and IR.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Hiperlipidemias/metabolismo , Resistencia a la Insulina , Trastornos del Metabolismo de los Lípidos/metabolismo , Metabolómica/métodos , Obesidad/metabolismo , Adulto , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/orina , Glucolípidos/metabolismo , Humanos , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/orina , Masculino , Espectrometría de Masas , Factores de Tiempo , Adulto Joven
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