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1.
Carbohydr Polym ; 300: 120249, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36372481

RESUMEN

Obesity-induced lipid metabolism disorders are risk factors for hyperlipidemia, atherosclerosis, and non-alcoholic fatty liver disease. Seaweed oligosaccharides and Zn supplements are potential alternatives to alleviate obesity. Herein, ulvan oligosaccharide (UO) was used as a ligand to prepare a novel Zn supplement (UO-Zn). Subsequently, we explored potential mechanisms underlying UO- and UO-Zn-mediated improvements in lipid metabolism in mice fed a high-fat diet. We found that UO enhanced the abundance of key species (Blautia and Turicibacter) and functions (glycolytic, pentose phosphate, and histidine/lysine biosynthesis pathways) in the gut microbiota, thereby increasing the production of short-chain fatty acids and activating AMPK. Accordingly, UO treatment regulated the transcription of lipid metabolism genes, including ACOX1, ACC, and FASN, thereby reducing blood lipid levels and hepatic lipid accumulation. Zn could act synergistically with UO, enhancing the reversal of cholesterol transport and fatty acid ß-oxidation via the MTF1/PPARα pathway, markedly reducing body and adipose tissue weights.


Asunto(s)
Dieta Alta en Grasa , Metabolismo de los Lípidos , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Zinc/farmacología , Oligosacáridos/farmacología , Oligosacáridos/metabolismo , Hígado , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Lípidos , Ratones Endogámicos C57BL
2.
Food Chem ; 402: 134232, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36137374

RESUMEN

Noni fruit has certain anti-obesity effect. However, the bioactive ingredients in noni fruit that contribute to anti-obesity activity as well as the relation between its anti-obesity activity and gut microbiota remain unclear. In this study, obese mice induced by high-fat diet (HFD) and were intervened with noni fruit phenolic extract (NFE) for 10 weeks. The results showed NFE supplementation decreased body weight, lipid accumulation in liver andadiposetissues, ameliorated gut microbiota dysbiosis by increasing short-chain fatty acid (SCFA)-producing bacteria and decreasing lipopolysaccharide (LPS)-producing bacteria, and mitigated intestinal inflammation and oxidative stress. Moreover, NFE supplementation improved intestinal barrier dysfunction by elevating the protein expression levels of Claudin-1, Occludin and ZO-1, alleviated the HFD-induced intestinal inflammation by repressing the LPS/TLR4/NF-κB pathway. Collectively, the findings revealed NFE intervention inhibits obesity by improving gut microbiota disorder, barrier function, and inflammation. Hence, NFE may be an effective way to ameliorate HFD-induced damage.


Asunto(s)
Microbioma Gastrointestinal , Morinda , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Morinda/metabolismo , Lipopolisacáridos/farmacología , Frutas/metabolismo , Ocludina/metabolismo , Receptor Toll-Like 4 , FN-kappa B/genética , Claudina-1/farmacología , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/genética , Obesidad/metabolismo , Ácidos Grasos Volátiles/metabolismo , Fenoles/farmacología , Inflamación/tratamiento farmacológico , Inflamación/genética , Extractos Vegetales/farmacología
3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1868(1): 159236, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36179802

RESUMEN

Diet-induced obesity (OB) is usually accompanied by hypertriglyceridemia, which is characterized by the accumulation of triglyceride (TG)-rich lipoprotein (TRL) particles in the circulation. We previously found that postprandial TRL combined with insulin induced the adipogenic differentiation of 3T3-L1 preadipocytes, which may represent a key mechanism underlying obesity. However, the specific mechanism and signaling pathway involved in this process remain to be fully elucidated. In this study, we found that, in the postprandial state, patients with obesity had significantly higher levels of TG and remnant cholesterol (RC) than normal-weight controls. In vitro, we found that postprandial TRL, together with insulin, promoted the adipogenic differentiation of adipose-derived mesenchymal stem cells (AMSCs), as evidenced by the increased expression of lipogenesis-related genes and their protein products, including low-density lipoprotein related protein 1 (LRP1). Besides, caveolin-1 (Cav-1) expression was also significantly upregulated under this condition. Cav-1 and LRP1 were observed to interact, and then led to the activation of the PI3K/AKT1 signaling pathway. Meanwhile, the inhibition of LRP1 or Cav-1 significantly attenuated the adipogenic differentiation of AMSCs and downregulated AKT1 phosphorylation levels. Moreover, treatment with a selective AKT1 inhibitor significantly suppressed postprandial TRL and insulin-induced adipogenesis in AMSCs. Combined, our results demonstrated that, in association with insulin, postprandial TRL can promote the adipogenic differentiation of AMSCs in a manner that is dependent on the LRP1/Cav-1-mediated activation of the PI3K/AKT1 signaling pathway. Our findings indicated that a postprandial increase in TRL content is a critical factor in the pathogenesis of hypertriglyceridemia and diet-induced obesity.


Asunto(s)
Hipertrigliceridemia , Células Madre Mesenquimatosas , Humanos , Adipogénesis , Caveolina 1/metabolismo , Triglicéridos/metabolismo , Lipoproteínas/metabolismo , Hipertrigliceridemia/complicaciones , Insulina/metabolismo , Obesidad/metabolismo , Lipoproteínas LDL/metabolismo , Células Madre Mesenquimatosas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo
4.
J Ethnopharmacol ; 301: 115824, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36273747

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.


Asunto(s)
Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Qigong , Animales , Femenino , Humanos , Ratones , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Modelos Animales de Enfermedad , Estradiol , Hipertrofia/patología , Inflamación/metabolismo , Insulina , Resistencia a la Insulina/fisiología , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Farmacología en Red , Factor 2 Relacionado con NF-E2/metabolismo , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico
5.
Physiology (Bethesda) ; 38(1): 0, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36125787

RESUMEN

"Precision nutrition" is an emerging area of nutrition research that focuses on understanding metabolic variability within and between individuals and helps develop customized dietary plans and interventions to maintain optimal individual health. It encompasses nutritional genomic (gene-nutrient interactions), epigenetic, microbiome, and environmental factors. Obesity is a complex disease that is affected by genetic and environmental factors and thus a relevant target of precision nutrition-based approaches. Recent studies have shown significant associations between obesity phenotypes (body weight, body mass index, waist circumference, and central and regional adiposity) and genetic variants, epigenetic factors (DNA methylation and noncoding RNA), microbial species, and environment (sociodemographics and physical activity). Additionally, studies have also shown that the interactions between genetic variants, microbial metabolites, and epigenetic factors affect energy balance and adiposity. These include variants in FTO, MC4R, PPAR, APOA, and FADS genes, DNA methylation in CpG island regions, and specific miRNAs and microbial species such as Firmicutes, Bacteriodes, Clostridiales, etc. Similarly, studies have shown that microbial metabolites, folate, B-vitamins, and short-chain fatty acids interact with miRNAs to influence obesity phenotypes. With the advent of next-generation sequencing and analytical approaches, the advances in precision nutrition have the potential to lead to new paradigms, which can further lead to interventions or customized treatments specific to individuals or susceptible groups of individuals. This review highlights the recent advances in precision nutrition as applied to obesity and projects the importance of precision nutrition in obesity and weight management.


Asunto(s)
MicroARNs , Obesidad , Humanos , Obesidad/genética , Obesidad/metabolismo , Nutrigenómica , Estado Nutricional , Dieta , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato
6.
J Steroid Biochem Mol Biol ; 225: 106198, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36181990

RESUMEN

To evaluate the effects of long-term vitamin D supplementation on metabolic profiles in middle-aged to elderly patients with type 2 diabetes (T2D), a randomized controlled trial was conducted among patients with T2D aged 50-70 years. A total of 270 patients underwent randomization with 135 being allocated to the vitamin D group and 135 to the control group, and participants in the vitamin D group received oral vitamin D3 (800 IU/day) for 30 months. Serum 25(OH)D and metabolic variables were measured at baseline, and after 6, 12, 18, and 30 months of intervention. After 30 months, the vitamin D group showed a greater increase in serum 25(OH)D than the control group (12.39 ± 6.99 vs 5.35 ± 5.29 ng/ml, P < 0.001). Meanwhile, changes in the levels of fasting insulin, HOMA-IR, non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and uric acid differed significantly between the two groups (all P < 0.05). Stratified analysis indicated that change in uric acid differed significantly between the two groups in subgroup with baseline 25(OH)D ≥ 20 ng/ml (P = 0.042) or subgroup with female patients (P = 0.034). And the change in fasting blood glucose (FBG) differed significantly between the vitamin D group (-0.30 ± 2.52 mmol/L) and the control group (0.49 ± 1.78 mmol/L, P = 0.049) among patients achieving 25(OH)D concentrations of 30 ng/ml at the end of this trial. A significant difference in the change of triglyceride was observed between the two groups among patients with obesity at baseline [0.05(-0.59, 0.23) vs 0.41(-0.01, 0.80) mmol/L, P = 0.023]. These findings suggested that long-term vitamin D supplementation significantly reduced fasting insulin, HOMA-IR, and serum concentrations of non-HDL-C, hs-CRP, and uric acid among middle-aged to elderly patients with T2D. And vitamin D status, gender, and baseline obesity may modify the effects of vitamin D supplementation.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Persona de Mediana Edad , Anciano , Humanos , Femenino , Vitamina D/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Proteína C-Reactiva/metabolismo , Ácido Úrico , Glucemia/metabolismo , Suplementos Dietéticos , Vitaminas/uso terapéutico , Insulina/metabolismo , Obesidad , Metaboloma , Método Doble Ciego
7.
Fam Community Health ; 46(1): 39-50, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36190961

RESUMEN

The typical pattern of weight change associated with behavioral obesity treatments has been some loss in weight through approximately 6 months, followed by near complete regain. However, patterns vary widely across individuals. The objectives are to determine whether recent prediction model-based indications of relations among changes in psychosocial correlates of the weight loss behaviors of physical activity and controlled eating vary by patterns of weight change. Women with obesity enrolled in a community-based behavioral obesity treatment who failed to lose at least 5% of their baseline weight (Minimal Effect group, n = 44), lost 5% or greater and then regained most during months 6 to 24 (Loss/Regain group, n = 42), or lost 5% or greater and then maintained/continued loss (Loss/Loss group n = 42) were evaluated. Improvements in physical activity- and eating-related self-regulation and self-efficacy, mood, and emotional eating over 6 months were significant overall and generally most favorable in the Loss/Loss group and least favorable in the Minimal Effect group. Expected model-based relationships between 6-month changes in the aforementioned psychosocial variables were significant and generally not significantly affected by weight change group. However, group substantially affected the prediction of self-regulation of eating at month 24-a key correlate of long-term weight loss. Findings suggested community-based obesity treatment targets and emphases.


Asunto(s)
Ingestión de Alimentos , Pérdida de Peso , Humanos , Femenino , Ingestión de Alimentos/psicología , Pérdida de Peso/fisiología , Obesidad/terapia , Obesidad/psicología , Autoeficacia , Ejercicio Físico/psicología , Conducta Alimentaria/psicología
8.
Artículo en Inglés | MEDLINE | ID: mdl-36316116

RESUMEN

BACKGROUND AND OBJECTIVES: To increase the validity of biomarker measures in multiple sclerosis (MS), factors affecting their concentration need to be identified. Here, we test whether the volume of distribution approximated by the patients' estimated blood volume (BV) and body mass index (BMI) affect the serum concentrations of glial fibrillary acidic protein (GFAP). As a control, we also determine the relationship between BV/BMI and GFAP concentrations in CSF. To confirm earlier findings, we test the same hypotheses for neurofilament light chain (NfL). METHODS: NfL and GFAP concentrations were measured in serum and CSF (sNFL/sGFAP and cNFL/cGFAP) in 157 patients (n = 106 with MS phenotype and n = 51 with other neurologic/somatoform diseases). Using multivariate linear regressions, BV was tested in the MS cohort as a predictor for each of the biomarkers while controlling for age, sex, MS phenotype, Expanded Disability Status Scale score, gadolinium-enhancing lesions, and acute relapse. In addition, overweight/obese patients (BMI ≥25 kg/m2) were compared with patients with BMI <25 kg/m2 using the general linear model. The analyses were repeated including the neurologic/somatoform controls. RESULTS: In the MS cohort, BV predicted sGFAP (ß = -0.301, p = 0.014). Overweight/obese patients with MS had lower sGFAP concentrations compared with patients with MS and BMI <25 kg/m2 (F = 4.732, p = 0.032). Repeating the analysis after adding patients with other neurologic/somatoform diseases did not change these findings (ß = -0.276, p = 0.009; F = 7.631, p = 0.006). Although sNfL was inversely correlated with BV (r = -0.275, p = 0.006) and body weight (r = -0.258, p = 0.010), those results did not remain significant after adjusting for covariates. BV and BMI were not associated with cGFAP or cNfL concentrations. DISCUSSION: These findings support the notion that the volume of distribution of sGFAP approximated by BV and BMI is a relevant variable and should therefore be controlled for when measuring sGFAP in MS, while this might not be necessary when measuring cGFAP concentrations.


Asunto(s)
Esclerosis Múltiple , Humanos , Proteína Ácida Fibrilar de la Glía , Filamentos Intermedios , Índice de Masa Corporal , Sobrepeso , Biomarcadores , Volumen Sanguíneo , Obesidad
9.
Mol Cell Endocrinol ; 559: 111813, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36341820

RESUMEN

Apolipoprotein A-IV (ApoA-IV) plays a role in satiation and serum lipid transport. In diet-induced obesity (DIO) C57BL/6J mice, ApoA-IV deficiency induced in ApoA-IV-/-knock-out (KO mice) resulted in increased bodyweight, insulin resistance (IR) and plasma free fatty acid (FFA), which was partially reversed by stable ApoA-IV-green fluorescent protein (KO-A4-GFP) transfection in KO mice. DIO KO mice exhibited increased M1 macrophages in epididymal white adipose tissue (eWAT) as well as in the blood. Based on RNA-sequencing analyses, cytokine-cytokine receptor interactions, T cell and B cell receptors, and especially IL-17 and TNF-α, were up-regulated in eWAT of DIO ApoA-IV KO compared with WT mice. Supplemented ApoA-IV suppressed lipopolysaccharide (LPS)-induced IKK and JNK phosphorylation in Raw264.7 macrophage cell culture assays. When the culture medium was supplemented to 3T3-L1 adipocytes they exhibited an increased sensitivity to insulin. ApoA-IV protects against obesity-associated metabolic inflammation mainly through suppression in M1 macrophages of eWAT, IL17-IKK and IL17-JNK activity.


Asunto(s)
Tejido Adiposo Blanco , Apolipoproteínas A , Ratones , Animales , Ratones Endogámicos C57BL , Adipocitos , Inflamación , Obesidad
10.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166564, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36181981

RESUMEN

OBJECTIVE: Obesity and its consequences are among the biggest challenges facing the healthcare system. Uterine leiomyomas are the most common gynecologic tumors. The risk of leiomyoma increases with obesity, but the underlying mechanisms of this association remain unclear. The aim of the present study to determine the cellular and molecular mechanisms by which adipocyte contributes to both leiomyoma tumor initiation and promotion. METHODS: Primary myometrium and leiomyoma cells were isolated from patients who underwent a hysterectomy or myomectomy. Pro-inflammatory, fibrotic, and angiogenic factors were measured using a multiplex cytokine array in human primary and immortalized myometrial and leiomyoma cells cocultured with human adipocyte (SW872) cells, or in animal ELT3 leiomyoma cells cocultured with 3 T3-L1 adipocytes. The free fatty acids (FFAs) and fatty acid-binding protein 4 (FABP4) levels were measured using immunofluorescence assays. Other protein abundances were determined using western blots. The expression levels of TNF-α, MCP-1, phospho-NF-κB, TGFß3 and VEGF-A in lean and obese in different leiomyoma patients were determined by immunofluorescence staining. RESULTS: Adipocytes promote inflammation, fibrosis, and angiogenesis in uterine leiomyoma cells by upregulating associated factors, such as IL-1ß, TNF-α, MCP-1, GM-CSF, TGF-ßs, PLGF, VEGF, HB-EGF, G-CSF and FGF2. Coculture led to the transfer of FFAs and FABP4 from adipocytes to leiomyoma cells, suggesting that adipocytes may modulate metabolic activity in these tumor cells. Increased levels of FFA and FABP4 expressions were detected in obese leiomyoma tissue compared to lean. The adipocyte-leiomyoma cell interaction increased the phospho-NF-κB level, which plays a key role in inflammation, restructuring metabolic pathways, and angiogenesis. Obese leiomyoma patients expressed a higher amount of TNF-α, MCP-1, phospho-NF-κB, TGFß3 and VEGF-A than lean leiomyoma patients, consistent with in vitro findings. Furthermore, we found that adipocyte secretory factors enhance leiomyoma cell proliferation by increasing PCNA abundance. Finally, the inhibition of the inflammatory factors TNF-α, MCP-1, and NF-κB abrogated the adipocyte coculture-induced proliferation of leiomyoma cells. CONCLUSIONS: Adipocytes release inflammatory, fibrotic, and angiogenic factors, along with FFAs, which contribute to a tumor-friendly microenvironment that may promote leiomyoma growth and can represent a new target for leiomyoma prevention and treatment.


Asunto(s)
Leiomioma , FN-kappa B , Humanos , Animales , Femenino , FN-kappa B/metabolismo , Técnicas de Cocultivo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adipocitos/metabolismo , Leiomioma/metabolismo , Leiomioma/patología , Inflamación/metabolismo , Obesidad/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Fibrosis , Microambiente Tumoral
11.
J Affect Disord ; 320: 319-329, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36183818

RESUMEN

BACKGROUND: Social and interpersonal context are associated with the onset and persistence of psychiatric disorders. We compared the effects of short-term interpersonal psychotherapy (IPT) on weight loss, binge eating behaviors, and depressive symptoms against cognitive-behavioral therapy (CBT), health education (HE), and behavioral weight loss (BWL). METHODS: We searched until May 28th, 2022 following databases: PubMed, CINAHL, Science Direct, Web of Science, EMBASE, and Scopus. Articles on parallel randomized clinical trials were included. Outcomes were body mass index (BMI), binge days (bulimic episode), and depressive symptoms. These outcomes were self-reported or measured with specific scales (BMI) or instrument (depressive symptoms). RESULTS: The initial search retrieved 820 articles, a total of 10 studies met the eligibility criteria, and seven were included in the meta-analysis. Participants with overweight/obesity were women (62-100 %), aged between 11 and 50 years. There was a trivial to small effect on BMI favoring IPT over other interventions (standardized mean difference [SMD] = -0.10; 95%CI: -0.27 to 0.07, I2 = 0 %), especially when compared to health education (SMD = -0.21; 95%CI: -0.54 to 0.12, I2 = 0 %); no effect on number of binge days (SMD = -0.09; 95%CI: -0.30 to 0.11, I2 = 0 %); and a small effect on depressive symptoms (SMD = -0.25, 95%CI = -0.50 to 0.00, I2 = 0 %). LIMITATIONS: Small number of studies, the discrepancy in age cohorts, and racial diversity. Psychotherapeutic protocols and assessment tools had to be adapted across studies. CONCLUSIONS: Patients with overweight/obesity and depression had some benefit from IPT when compared with other interventions. In view of existing evidence, an IPT program adapted to obesity could help to achieve reliable and long-term effects.


Asunto(s)
Psicoterapia Interpersonal , Psicoterapia , Humanos , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Psicoterapia/métodos , Sobrepeso/terapia , Obesidad/terapia , Obesidad/psicología , Pérdida de Peso
12.
J Affect Disord ; 320: 397-403, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36206878

RESUMEN

BACKGROUND: The comorbidity of obesity and major depressive disorder (MDD) may be attributable to a bidirectional relationship and shared genetic influence. We aimed to examine the polygenic associations between obesity and MDD and to characterize their corresponding impacts on the obesity mechanism. METHODS: Genome-wide genotyping was available in 106,604 unrelated individuals from Taiwan Biobank. Polygenic risk score (PRS) for body mass index (BMI) and MDD was derived to evaluate their effects on obesity-related traits. Stratified analyses were performed for the modified effect of depression on the polygenic associations. RESULTS: The MDD PRS was positively associated with waistline (beta in per SD increase in PRS = 0.12), hipline (beta = 0.08), waist-hip ratio (WHR) (beta = 0.05), body fat rate (beta = 0.08), BMI (beta = 0.05), overweight (OR = 1.02 for BMI ≥ 25), and obesity (OR = 1.05 for BMI ≥ 30). For the synergism between depression and BMI PRS, the presence of active depression symptoms defined by the PHQ-4 (p for interaction < 0.05 for waistline, WHR, and BMI) was more salient than lifetime MDD. LIMITATIONS: Limitations include recall bias for MDD due to a retrospective self-reporting questionnaire, a low response rate of the PHQ-4 for evaluating active psychological symptoms, and limited generalizability to non-Taiwanese ancestries. CONCLUSIONS: The shared genetic etiology of obesity and depression was demonstrated. The amplified effect of BMI polygenic effect on obesity for individuals with active depressive symptoms was also characterized. The study may be helpful for designing public health interventions to reduce the disease burden caused by obesity and depression.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/diagnóstico , Bancos de Muestras Biológicas , Depresión/epidemiología , Depresión/genética , Estudios Retrospectivos , Predisposición Genética a la Enfermedad , Herencia Multifactorial , Obesidad/epidemiología , Obesidad/genética , Obesidad/diagnóstico , Estudio de Asociación del Genoma Completo
13.
Artículo en Inglés | MEDLINE | ID: mdl-36209772

RESUMEN

Compulsive overeating of palatable food is thought to underlie some forms of obesity. Similarities are often observed in the behavioural symptomology and the neuropathophysiology underlying substance use disorder and compulsive overeating. As such, preclinical animal models which assess addiction-like behaviour towards food may assist the understanding of the neurobiology underlying overeating behaviour. Further, the relationship between these behaviours and the propensity for diet-induced obesity warrants examination. In this study we investigated the relationship between the propensity for diet-induced obesity (DIO) and addiction-like behaviour towards highly palatable food in C57BL/6 J mice as measured by a 3-criteria model. We also examined the extent to which performance on this 3-criteria model predicted two key hallmark features of addiction - resistance to extinction and relapse propensity (as measured by reinstatement of lever pressing). C57BL/6 J mice were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions whereby addiction-like behaviour towards a high-fat high-sugar food reward was assessed using a 3-criteria model similar to that used to assess addiction-like behaviour towards drugs of abuse. In contrast to findings in rats, no difference in addiction-like behaviour towards food was observed between obesity prone (OP) and obesity resistant (OR) mice. Similarly, principal components analysis found no distinct patterns in the relationship between addiction-like behaviours across treatment groups. This suggests that the strain and species of rodent may be critical for studying the mechanisms underlying pathological overconsumption. Further analysis revealed that the extent of performance on the 3-criteria model correlated with the propensity for C57BL/6 J mice to both extinguish food seeking behaviour and "relapse" after a period of withdrawal. This finding was evident across all groups, regardless of DIO. Collectively, these data validate the 3-criteria model as a robust model to comprehensively assess food addiction-like behaviour in mice, regardless of prior food intake history.


Asunto(s)
Conducta Adictiva , Azúcares , Ratas , Animales , Ratones , Ratones Endogámicos C57BL , Obesidad , Hiperfagia , Conducta Alimentaria
14.
Synapse ; 77(1): e22254, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36099576

RESUMEN

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.


Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Radiofármacos , Humanos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Sobrepeso , Obesidad/diagnóstico por imagen , Receptores de Dopamina D2/metabolismo
15.
J Ethnopharmacol ; 300: 115633, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36031104

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Lagenaria siceraria Stand. (Family: Cucurbitaceae), popularly known as bottle gourd, is traditionally used in Ayurvedic medicine as a food plant, especially in hypertension and obesity. AIM OF THE STUDY: Investigations were undertaken to assign novel lead combinations from this common food plant to multi-molecular modes of actions in the complex disease networks of obesity and hypertension. LC-MS/MS based metabolite screening, in-vivo high fat diet induced hyperlipidemia animal study and network pharmacology explorations of the mechanism of action for lipid lowering effects including a neighbourhood community approach for molecular combinations were performed. MATERIAL AND METHODS: Major chemical constituents of the fruits of LS (LSFE) were analysed by HPLC-DAD-MS/MS-QTOF. Wistar albino rats (n = 36), divided into 6 groups (n = 6) received either no treatment or a high-fat diet along with LSFE or Atorvastatin. Lipid profiles and biochemical parameters were evaluated. In silico cross-validated network analyses using different databases and Cytospace were applied. RESULTS: Profiling of LSFE revealed 18 major constituents: phenolic acids like p-Coumaric acid and Ferulic acid, the monolignolconferyl alcohol, the flavonoid glycosides hesperidin and apigenin-7-glucoside. Hyperlipidemic animals treated with LSFE (200 mg/kg, 400 mg/kg, 600 mg/kg) showed a significant improvement of their lipid profiles after 30 days of treatment. Network pharmacology analyses for the major 18 compounds revealed enrichment of the insulin and the ErbB signalling pathway. Novel target node combinations (e.g. AKR1C1, AGXT) including their connection to different pathways were identified in silico. CONCLUSIONS: The combined in vivo and bioinformatics analyses propose that lead compounds of LSFE act in combination on relevant targets of hyperlipidemia. Perturbations of the IRS→Akt→Foxo1 cascade are predicted which suggest further clinical investigation towards development of safe natural alternative to manage hyperlipidemia.


Asunto(s)
Cucurbita , Hesperidina , Hiperlipidemias , Hipertensión , Insulinas , Animales , Atorvastatina , Cromatografía Liquida , Flavonoides/uso terapéutico , Glicósidos/uso terapéutico , Hesperidina/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Insulinas/uso terapéutico , Farmacología en Red , Obesidad/tratamiento farmacológico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-akt , Espectrometría de Masas en Tándem
16.
J Ethnopharmacol ; 300: 115680, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36058479

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome (MetS) is a cluster of disease centered on obesity, which is the result of stagnation of liver qi according to traditional Chinese medicine. Panax notoginseng is a traditional Chinese herbal medicine, entering liver and stomach meridians and dissipating blood stasis, in which panax notoginseng saponins (PNS) are the main active components. However, its effects and mechanism on metabolic syndrome has not been revealed yet. AIM OF STUDY: To evaluate the anti-MetS effect of PNS, including body weight and adiposity, glucose metabolism and non-alcoholic fatty liver disease (NAFLD), as well as to explore the mechanism and signaling pathway of PNS on MetS effect. MATERIALS AND METHODS: HPLC was utilized to affirm the percentages of saponins in PNS. In vivo, normal C57BL/6J mice and high-fat diet (HFD)-induced MetS mice were used to evaluate anti-MetS effect of PNS. Body weight, food and water intake were recorded. NMR imager was used for NMR imaging and lipid-water analysis. Blood glucose detection, glucose and insulin tolerance test were performed to evaluate glucose metabolism. Biochemical indexes analysis and histopathological staining were used to evaluate the effect on NAFLD. The expressions of mRNA and proteins related to thermogenesis in adipose tissue were determined using real-time PCR and Western blot. In silico, network pharmacology was utilized to predict potential mechanism. In vitro, matured 3T3-L1 adipocyte was used as subject to confirm the signaling pathway by Western blot. RESULTS: We determined the content of PNS component by HPLC. In vivo, PNS could improve metabolic syndrome with weight loss, reduction of adiposity, improvement of adipose distribution, correction of glucose metabolism disorder and attenuation of NAFLD. Mechanismly, PNS boosted energy exhaustion and dramatically enhanced thermogenesis in brown adipose tissue (BAT), induced white adipose tissue (WAT) browning. In silico, utilizing network pharmacology strategy, we identified 307 candidate targets which were enriched in MAPK signaling pathway specifically in liver tissue and adipocyte. In vitro validation confirmed ERK and p38MAPK mediated anti-MetS effects of PNS, not JNK signaling pathway. CONCLUSION: PNS exerted protective effect on metabolic syndrome through MAPK-mediated adipose thermogenic activation, which may serve as a prospective therapeutic drug for metabolic syndrome.


Asunto(s)
Medicamentos Herbarios Chinos , Insulinas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Panax notoginseng , Saponinas , Animales , Glucemia , Peso Corporal , Medicamentos Herbarios Chinos/farmacología , Glucosa , Lípidos , Síndrome Metabólico/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Farmacología en Red , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Panax notoginseng/química , ARN Mensajero/metabolismo , Saponinas/farmacología , Saponinas/uso terapéutico , Agua
17.
Braz. j. biol ; 83: e251198, 2023. tab, graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1339350

RESUMEN

Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.


Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.


Asunto(s)
Animales , Ratas , Asteraceae , Antioxidantes , Daño del ADN , Extractos Vegetales/farmacología , Ratas Wistar , Obesidad/tratamiento farmacológico
19.
J Environ Sci (China) ; 124: 472-480, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36182155

RESUMEN

Antibiotics have been identified as obesogens contributing to the prevalence of obesity. Moreover, their environmental toxicity shows sex dependence, which might also explain the sex-dependent obesity observed. Yet, the direct evidence for such a connection and the underlying mechanisms remain to be explored. In this study, the effects of tetracycline, which is a representative antibiotic found in both environmental and food samples, on Drosophila melanogaster were studied with consideration of both sex and circadian rhythms (represented by the eclosion rhythm). Results showed that in morning-eclosed adults, tetracycline significantly stimulated the body weight of females (AM females) at 0.1, 1.0, 10.0 and 100.0 µg/L, while tetracycline only stimulated the body weight of males (AM males) at 1.0 µg/L. In the afternoon-eclosed adults, tetracycline significantly stimulated the body weight of females (PM females) at 0.1, 1.0 and 100.0 µg/L, while it showed more significant stimulation in males (PM males) at all concentrations. Notably, the stimulation levels were the greatest in PM males among all the adults. The results showed the clear sex dependence of the obesogenic effects, which was diminished by dysrhythmia. Further biochemical assays and clustering analysis suggested that the sex- and rhythm-dependent obesogenic effects resulted from the bias toward lipogenesis against lipolysis. Moreover, they were closely related to the preference for the energy storage forms of lactate and glucose and also to the presence of excessive insulin, with the involvement of glucolipid metabolism. Such relationships indicated potential bridges between the obesogenic effects of pollutants and other diseases, e.g., cancer and diabetes.


Asunto(s)
Contaminantes Ambientales , Compuestos Heterocíclicos , Insulinas , Animales , Antibacterianos/farmacología , Peso Corporal , Ritmo Circadiano , Drosophila melanogaster , Femenino , Glucosa , Insulinas/farmacología , Lactatos/farmacología , Masculino , Obesidad/inducido químicamente , Tetraciclina/toxicidad
20.
J Affect Disord ; 320: 241-246, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36162686

RESUMEN

BACKGROUND: Evidence of associations between psychological symptoms and tumor necrosis factor (TNF)-α level is scant, as is evidence on sex differences in associations for children and adolescents with obesity. This study examined sex differences in associations between psychological symptoms (self-concept, anxiety, depression, anger, and disruptive behavior) and TNF-α level in Taiwanese children and adolescents with healthy weight, overweight, or obesity. METHODS: In 2010, 564 first, fourth, and seventh graders-comprising 250 children with overweight or obesity (44.3 %), 330 adolescents (58.5 %), and 303 males (53.7 %)-underwent a health examination and blood sampling and completed a questionnaire. RESULTS: A significantly higher TNF-α level was found in children and adolescents with healthy weight than in those with overweight or obesity (median: 14.5 vs. 4.1 (pg/mL); p < 0.001). In multiple linear regression models, anxiety was significantly positively associated with TNF-α level in female participants with healthy weight (ß = 0.11 per 10 increments in anxiety, 95 % confidence interval = 0.01-0.22). LIMITATIONS: Given the cross-sectional nature of the study, no inferences of causal relationships among TNF-α level, obesity, and psychological symptoms could be made. CONCLUSIONS: The findings enrich the literature on the TNF-α-psychological symptom association. Sex differences were found in children and adolescents without obesity rather than in those without obesity, and a higher TNF-α level was associated with increased anxiety in girls without obesity. The role of sex differences in the complex associations among psychological symptoms, TNF-α level, and overweight or obesity requires further investigation.


Asunto(s)
Sobrepeso , Factor de Necrosis Tumoral alfa , Humanos , Niño , Adolescente , Femenino , Masculino , Sobrepeso/psicología , Estudios Transversales , Caracteres Sexuales , Taiwán/epidemiología , Obesidad/epidemiología , Índice de Masa Corporal
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