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2.
Pediatr Endocrinol Rev ; 17(1): 4-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599132

RESUMO

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Resistência à Insulina , Lipólise , Tecido Adiposo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Lipólise/efeitos dos fármacos
3.
J Agric Food Chem ; 67(38): 10595-10603, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475817

RESUMO

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , beta-Criptoxantina/administração & dosagem , Obesidade/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Proteína Desacopladora 1/genética , Animais , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Receptores do Ácido Retinoico/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
4.
BMC Infect Dis ; 19(1): 708, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399063

RESUMO

BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) are associated with long-lasting adipose tissue redistribution. Adiponectin is a widely used marker of adipocyte activity, and adipose tissue density assessed by CT-scan is associated with adipocyte size and function. We hypothesized that prior exposure to TA and ddI was associated with long-lasting adipose tissue dysfunction in people living with HIV (PLWH). Thus, we tested possible associations between markers of adipose tissue dysfunction (adipose tissue density and adiponectin) and prior exposure to TA and/or ddI, years after treatment discontinuation. METHODS: Eight hundred forty-eight PLWH from the COCOMO study were included and stratified according to prior exposure to TA and/or ddI (with, n = 451; without n = 397). Visceral (VAT) and subcutaneous (SAT) adipose tissue area and density were determined by single slice abdominal CT-scan at lumbar 4th level. Venous blood was collected and analyzed for adiponectin. Multivariable linear and logistic regression analyses were used to test our hypotheses. Multivariable models were adjusted for age, sex, smoking, origin, physical activity, BMI, and adipose tissue area (VAT or SAT area, accordingly to the outcome). RESULTS: prior exposure to TA and/or ddI was associated with excess risk of low VAT (adjusted OR (aOR) 1.74 [1.14; 2.67]) and SAT density (aOR 1.74 [1.18; 2.58]), for a given VAT and SAT area, respectively. No association between VAT and SAT density with time since TA and/or ddI discontinuation was found. 10 HU increase in VAT density was associated with higher adiponectin plasma level and this association was not modified by prior exposure to TA and/or ddI. Prior exposure to TA and/or ddI was associated with 9% lower [- 17;-2] plasma adiponectin levels and with excess risk of low adiponectin (aOR 1.74 [1.10; 2.76]). CONCLUSIONS: We described low adipose tissue density and impaired adiponectin production to be associated with prior exposure to TA and/or ddI even years after treatment discontinuation and independently of adipose tissue area. These findings suggest that prior TA and ddI exposure may have long-lasting detrimental effects on adipose tissue function and, consequently, on cardiometabolic health in PLWH.


Assuntos
Adiponectina/sangue , Tecido Adiposo/efeitos dos fármacos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Tecido Adiposo/patologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Didanosina/efeitos adversos , Feminino , Infecções por HIV/fisiopatologia , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/efeitos dos fármacos , Timidina/análogos & derivados
5.
Endocrinology ; 160(10): 2367-2387, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265057

RESUMO

Prolonged exposure to glucocorticoids (GCs) causes various metabolic derangements. These include obesity and insulin resistance, as inhibiting glucose utilization in adipose tissues is a major function of GCs. Although adipose tissue distribution and glucose homeostasis are sex-dependently regulated, it has not been evaluated whether GCs affect glucose metabolism and adipose tissue functions in a sex-dependent manner. In this study, high-dose corticosterone (rodent GC) treatment in C57BL/6J mice resulted in nonfasting hyperglycemia in male mice only, whereas both sexes displayed hyperinsulinemia with normal fasting glucose levels, indicative of insulin resistance. Metabolic testing using stable isotope-labeled glucose techniques revealed a sex-specific corticosterone-driven glucose intolerance. Corticosterone treatment increased adipose tissue mass in both sexes, which was reflected by elevated serum leptin levels. However, female mice showed more metabolically protective adaptations of adipose tissues than did male mice, demonstrated by higher serum total and high-molecular-weight adiponectin levels, more hyperplastic morphological changes, and a stronger increase in mRNA expression of adipogenic differentiation markers. Subsequently, in vitro studies in 3T3-L1 (white) and T37i (brown) adipocytes suggest that the increased leptin and adiponectin levels were mainly driven by the elevated insulin levels. In summary, this study demonstrates that GC-induced insulin resistance is more severe in male mice than in female mice, which can be partially explained by a sex-dependent adaptation of adipose tissues.


Assuntos
Glicemia/metabolismo , Corticosterona/toxicidade , Resistência à Insulina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Insulina/farmacologia , Leptina/genética , Leptina/metabolismo , Masculino , Camundongos , Fatores Sexuais
6.
Expert Opin Drug Saf ; 18(9): 829-840, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31304808

RESUMO

Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Doenças Metabólicas/induzido quimicamente , Tecido Adiposo/efeitos dos fármacos , Fármacos Anti-HIV/administração & dosagem , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Glucose/metabolismo , Humanos , Estilo de Vida , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/epidemiologia , Fatores de Risco
7.
Biomed Environ Sci ; 32(6): 406-418, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262386

RESUMO

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.


Assuntos
Autofagia/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , TYK2 Quinase/metabolismo
8.
J Drugs Dermatol ; 18(7): 675-680, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334926

RESUMO

Introduction: Injectable deoxycholic acid (DCA; Kybella; Allergan, Irvine, CA) is currently approved only for treatment of persistent submental fat (SMF). Many cosmetic surgeons use DCA off-label to treat fat tissue in other areas of the body. There is no review summarizing the off-label uses of injectable DCA. Methods: A systematic literature search was conducted through PubMed, Cochrane, CINAHL, and Web of Science databases using search terms "ATX-101 OR Kybella OR deoxycholic OR deoxycholate NOT amphotericin NOT bile" in accordance to PRISMA guidelines to identify off-label uses for injectable DCA or ATX-101. Results: Ten pertinent articles were identified for review. Anatomic areas treated include the face, brassiere line, foot, and gluteotrochanteric region. Indications include facial contouring, paradoxical adipose hyperplasia, HIV/HAART-associated buccal fat pad lipodystrophy, and reduction of lipomatous tumors. DCA is efficacious at causing lipolysis and safe with minimal side effects. Most patients treated for cosmetic indications reported high patient satisfaction. Conclusion: Off-label use of injectable DCA demonstrate a similar safety profile, effectiveness, and overall patient satisfaction compared to FDA-approved use for persistent SMF. DCA appears to be a safe and efficacious alternative to surgical reduction of unwanted adipose tissue in non-submental areas. Larger-scale studies are warranted to explore further cosmetic and potential medical applications. J Drugs Dermatol. 2019;18(7):675-680.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Técnicas Cosméticas/efeitos adversos , Ácido Desoxicólico/administração & dosagem , Uso Off-Label , Nádegas , Ácido Desoxicólico/efeitos adversos , Estética , Face , , Humanos , Injeções Subcutâneas/efeitos adversos , Lipólise/efeitos dos fármacos , Satisfação do Paciente , Resultado do Tratamento
9.
Cell Physiol Biochem ; 53(1): 62-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184447

RESUMO

BACKGROUND/AIMS: Skeletal muscle injuries are the most common type of injury occurring in sports, and investigating skeletal muscle regeneration as well as understanding the related processes is an important aspect of the sports medicine field. The process of regeneration appears to be complex and precisely orchestrated, involving fibro-adipogenic progenitors (FAPs) which are a muscle-resident stem cell population that appears to play a major role in abnormal development of fibrotic tissue or intermuscular adipose tissue (IMAT). Our present study aims to investigate whether muscle resting or endurance exercise following muscle injury may change the behavior of FAPs and subsequently impact the development of fatty infiltrations and fibrosis, two hallmarks of regeneration failure. METHODS: We used the validated glycerol muscle injury model to mimic abnormal muscle regenerative conditions in mice. We challenged this specific regeneration model with hindlimb unloading or endurance exercise and, in a second set of experiments, we treated mice with decorin, a TGF-ß inhibitor. RESULTS: In this study, we demonstrated that: i) muscle resting just after injury leads to inhibition of IMAT development, ii) TNF-α mediated FAP apoptosis might be perturbed in this specific glycerol model of muscle injury, leading to IMAT development, and iii) treatment with the TGF-ß inhibitor decorin decreases IMAT development and might restores FAP apoptosis. CONCLUSION: In addition to the potential clinical relevance of decorin treatment in situations involving muscle plasticity and regeneration, this study also demonstrates that a period of muscle resting is necessary following muscle injury to achieve efficient muscle regeneration which is associated with a reduction in fatty infiltration. Unreasonably early resumption of exercise brings no gain to regeneration, further highlighting that this resting period is necessary.


Assuntos
Decorina/uso terapêutico , Músculo Esquelético/lesões , Doenças Musculares/tratamento farmacológico , Fator de Crescimento Transformador beta/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Decorina/farmacologia , Feminino , Glicerol/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/patologia , Condicionamento Físico Animal , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/metabolismo
10.
Int J Mol Sci ; 20(12)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234600

RESUMO

Obesity is a serious health challenge worldwide and is associated with various comorbidities, including dyslipidemia, type 2 diabetes, and cardiovascular disease. Developing effective strategies to prevent obesity is therefore of paramount importance. One potential strategy to reduce obesity is to consume calcium, which has been implicated to be involved in reducing body weight/fat. In this review, we compile the evidence for the anti-obesity roles of calcium in cells, animals, and humans. In addition, we summarize the possible anti-obesity mechanisms of calcium, including regulation of (a) adipogenesis, (b) fat metabolism, (c) adipocyte (precursor) proliferation and apoptosis, (d) thermogenesis, (e) fat absorption and excretion, and (f) gut microbiota. Although the exact anti-obesity roles of calcium in different subjects and how calcium induces the proposed anti-obesity mechanisms need to be further investigated, the current evidence demonstrates the anti-obesity effects of calcium and suggests the potential application of dietary calcium for prevention of obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cálcio na Dieta/farmacologia , Suplementos Nutricionais , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Termogênese/efeitos dos fármacos
11.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075962

RESUMO

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.


Assuntos
Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Resistência à Insulina , Lignanas/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Compostos de Bifenilo/farmacologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/sangue , Dislipidemias/complicações , Fígado Gorduroso/sangue , Fígado Gorduroso/complicações , Fígado Gorduroso/patologia , Comportamento Alimentar/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Leptina/sangue , Lignanas/farmacologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos
12.
Int J Mol Sci ; 20(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083300

RESUMO

TCDD-inducible poly-ADP-ribose polymerase (TIPARP) is an aryl hydrocarbon receptor (AHR) target gene that functions as part of a negative feedback loop to repress AHR activity. Tiparp-/- mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including lethal wasting syndrome. However, it is not known whether Tiparp-/- mice also exhibit increased sensitivity to other AHR ligands. In this study, we treated male Tiparp-/- or wild type (WT) mice with a single injection of 100 mg/kg 3-methylcholanthrene (3MC). Consistent with TIPARP's role as a repressor of AHR signaling, 3MC-treated Tiparp-/- mice exhibited increased hepatic Cyp1a1 and Cyp1b1 levels compared with WT mice. No 3MC-treated Tiparp-/- mice survived beyond day 16 and the mice exhibited chylous ascites characterized by an accumulation of fluid in the peritoneal cavity. All WT mice survived the 30-day treatment and showed no signs of fluid accumulation. Treated Tiparp-/- mice also exhibited a transient and mild hepatotoxicity with inflammation. 3MC-treated WT, but not Tiparp-/- mice, developed mild hepatic steatosis. Lipid deposits accumulated on the surface of the liver and other abdominal organs in the 3MC-Tiparp-/- mice. Our study reveals that Tiparp-/- mice have increased sensitivity to 3MC-induced liver toxicity, but unlike with TCDD, lethality is due to chylous ascites rather than wasting syndrome.


Assuntos
Ascite Quilosa/induzido quimicamente , Ascite Quilosa/enzimologia , Metilcolantreno/toxicidade , Poli(ADP-Ribose) Polimerases/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Compostos Azo/farmacologia , Ascite Quilosa/patologia , Citocinas/metabolismo , Fígado Gorduroso/enzimologia , Fígado Gorduroso/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos Knockout , Poli(ADP-Ribose) Polimerases/genética , Pirazóis/farmacologia , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Análise de Sobrevida
13.
J Anim Sci ; 97(6): 2631-2643, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31073599

RESUMO

Omega-3 long chain fatty acids have a positive impact on production. When consumed during late gestation, it might have fetal programming effects on the fetus, which will have lifelong impacts on development and production. The objectives of the present study were to evaluate the effect of increasing doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet of ewes in the last third of gestation on their body weight (BW), subcutaneous adipose tissue relative mRNA abundance of genes associated with adipose tissue metabolism, and growth performance and plasma metabolites and hormones of their offspring during the finishing phase. Ewes (n = 72) were blocked by BW and allotted to pens (8 per treatment) with 3 ewes per pen. Ewes were supplemented with an EPA and DHA source (Strata G113) at concentrations of 0, 1, or 2% of dry matter intake during the last 50 d of gestation. At lambing, all ewes were penned together and offered the same diet. After weaning at 60 d of age, lambs were blocked by BW and sex and fed for 56 d. All lambs were fed the same pellet diet (61.09% ground corn, 24.08% soy hulls, 11.09% soybean meal, 1.48% Ca salt of palm oil, and 2.26% mixed mineral vitamin), and were weighed every 14 d until the end of the trial. Blood samples were collected on the weight sampling days. Dry matter intake and refusals were weighed daily. Data were analyzed as a randomized complete block design with repeated measurements (SAS 9.4). Polynomial contrast (linear-L and quadratic-Q) was used for mean separation. There were no differences in ewe body condition score, milk production, milk fat, or milk protein, but there was a trend for increased (L, P = 0.06) lactose concentration, and also differences in DGAT1 (L, P = 0.04), Δ5-desaturase (Q, P = 0.06) and Δ6-desaturase (Q, P = 0.07), PPARα (Q, P = 0.03), ELOVL2 and 5 (Q, P < 0.07), FABP4 (Q, P = 0.04), FATP1 (Q, P = 0.06), leptin (Q, P = 0.02), and resistin (L, P = 0.05). Feeding pregnant ewes an increased amount of EPA and DHA in late gestation increased final BW (L, P = 0.01), ADG (L, P = 0.04; Q, P = 0.01), DMI (Q, P ≤ 0.01), plasma glucose concentration (L, P = 0.04), and trended to decrease ghrelin concentrations (L, P = 0.07) in offspring during the finishing period. Dam supplementation did not affect G:F, nor plasma NEFA concentration (P ≥ 0.53) of lambs. Therefore, increasing supplementation of EPA and DHA in pregnant ewes has an impact on offspring performance, increasing DMI, ADG, and BW.


Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análogos & derivados , Grelina/análise , Ovinos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Ácido Eicosapentaenoico/farmacologia , Feminino , Gravidez , Desmame
14.
Molecules ; 24(9)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035535

RESUMO

Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage.


Assuntos
Anti-Inflamatórios/farmacologia , Euterpe/química , Frutas/química , Polifenóis/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios/química , Biomarcadores , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , NF-kappa B/metabolismo , Polifenóis/química , Ratos , Transdução de Sinais/efeitos dos fármacos
15.
J Anim Sci ; 97(7): 3071-3088, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31063536

RESUMO

The objective of this study was to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation to ewes during late gestation on finishing lamb liver and adipose tissue fatty acid (FA) profile and gene expression. Lambs born from ewes supplemented with Ca salts of EPA + DHA, or palm FA distillate (PFAD) high in palmitic and oleic acid at 0.39% DM during the last 50 d of gestation were used. Lambs were weaned at 61 d of age and adapted to a high concentrate diet for 1.5 mo. After adaptation, 74 lambs (28 pens) were blocked by sex and BW and used in a 2 × 2 factorial arrangement of treatments using the factors of dam supplementation (DS) and lamb supplementation (LS) of Ca salts of EPA + DHA or PFAD at 1.48% DM. Lambs were slaughtered after 42 d and liver and adipose tissue collected for FA and gene expression analysis. Liver concentrations of EPA and DHA were greater (P < 0.01) with LS of EPA + DHA vs. PFAD during the finishing period. In adipose tissue, a lamb × dam interaction was observed for EPA (P = 0.02) and DHA (P = 0.04); LS of EPA + DHA increased EPA and DHA, but the increase was greatest in lambs born from ewes supplemented with PFAD. No lamb × dam treatment interactions were observed for gene expression in liver tissue (P > 0.10). Hepatic mRNA abundance of hormone-sensitive lipase (HSL; P = 0.01) was greater in lambs born from EPA + DHA ewes vs. lambs from PFAD ewes. mRNA expression of stearoyl-CoA desaturase (P < 0.01), fatty acid synthase (P = 0.01), Δ5-desaturase (P < 0.01), and Δ6-desaturase (P < 0.01) were decreased in liver of EPA + DHA lambs. A significant lamb × dam diet interaction was observed for elongation of very long chain fatty acid 2 in adipose tissue (P = 0.01); lambs supplemented with the same FA as their dams had lower expression. Expression of HSL tended (P = 0.08) to be decreased in adipose of EPA + DHA lambs born from EPA + DHA ewes. The changes in mRNA expression suggest that lipogenesis decreased, and lipolysis increased in lamb liver with EPA + DHA vs. PFAD supplementation during the finishing period. In adipose tissue, changes suggest that lipogenesis decreased in lambs born from EPA + DHA supplemented dams and supplemented with EPA + DHA during the finishing period. In addition, these results suggest an interaction between supplementation of FA to dams during late gestation on lamb response of adipose tissue, but not liver, to FA supplementation during the finishing period.


Assuntos
Suplementos Nutricionais/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/farmacologia , Ovinos/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Ração Animal/análise , Animais , Cálcio/farmacologia , Dieta/veterinária , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos não Esterificados/metabolismo , Feminino , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Parto/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Ovinos/genética , Desmame
16.
J Food Sci ; 84(4): 717-725, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30977920

RESUMO

The study aimed to explore the metabolic changes of adipose tissue of hyperlipidemia rats with hawthorn ethanol extracts (HEE) consumption by a high-throughput metabolomics approach. HEE were mainly composed of chlorogenic acid, hyperoside, isoquercitrin, rutin, vitexin, quercetin, and apigenin by HPLC analysis. HEE administration significantly lowered levels of the total cholesterols, triglyceride and low-density lipoprotein cholesterol as compared to the high-fat diet model. Gas chromatography-mass spectrometry was used to identify adipose metabolite profiles. Numerous endogenous molecules were altered by high-fat diet and restored following intervention of HEE. Metabolites elevated in adipose, including l-threonine, aspartic acid, glutamine, mannose, inositol and oleic acid, were detected after HEE consumption. Fifteen metabolites were identified as potential biomarkers of hyperlipidemia. Pathway analysis showed that most of the discriminant metabolites were included in fatty acid biosynthesis, galactose metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, glycerolipid metabolism and steroid biosynthesis. These metabolites and metabolic networks we found offer new insights into exploring the molecular mechanisms of lipid-lowering of hawthorn ethanol extracts on adipose tissue of rats. PRACTICAL APPLICATION: There was a very high proportion of hyperlipidemia in China. Hawthorn is attracting increasing attention owing to their health benefits, low toxicity, effectiveness and might be suitable for long-term use.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Crataegus/química , Hiperlipidemias/metabolismo , Metabolômica/métodos , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Etanol/química , Metabolismo dos Lipídeos , Metaboloma/efeitos dos fármacos , Ratos
17.
Nat Immunol ; 20(5): 581-592, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962591

RESUMO

Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation.


Assuntos
Inflamação/imunologia , Macrófagos/imunologia , Obesidade/imunologia , Receptores Acoplados a Proteínas-G/imunologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação/genética , Inflamação/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Obesidade/genética , Obesidade/metabolismo , Receptores Acoplados a Proteínas-G/deficiência , Receptores Acoplados a Proteínas-G/genética , Ácido Succínico/imunologia , Ácido Succínico/metabolismo , Ácido Succínico/farmacologia , Células THP-1
18.
Mol Med Rep ; 19(6): 4797-4805, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957183

RESUMO

Perivascular adipose tissue (PVAT) is considered to serve a vital role during the development of endothelial dysfunction. The current study investigated the effect of exosomes derived from mangiferin­stimulated PVAT on endothelial function, including regeneration, migration, apoptosis and inflammation. The number of exosomes secreted by PVAT was increased by stimulation with mangiferin (0.1, 1 or 10 µM), and uptake of these exosomes by endothelial cells was observed. Exosomes produced by stimulation of PVAT with mangiferin reversed the effects of inflammation­induced endothelial dysfunction following palmitic acid (PA) treatment. Furthermore, nuclear factor (NF)­κB signaling in endothelial cells was significantly increased when treated with PA­induced PVAT­derived exosomes, whereas exosomes from the supernatant of PVAT stimulated with mangiferin reduced p65 and p50 phosphorylation levels in the cells, and inhibited p65 transportation to the nucleus. Taken together, the present study demonstrated that exosomes derived from mangiferin­stimulated PVAT supernatant inhibited inflammation­induced endothelial dysfunction via modulation of NF­κB signaling.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Exossomos/metabolismo , Doenças Vasculares/metabolismo , Xantonas/farmacologia , Tecido Adiposo/patologia , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Inflamação , Masculino , NF-kappa B , Ácido Palmítico/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
19.
In Vivo ; 33(3): 707-715, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028187

RESUMO

BACKGROUND/AIM: The rapid increase in the number of people who are overweight or obese, which increases the risk of diseases and health problems, is becoming an important issue. Herein, we investigated whether olive leaf extract (OLE) has potent anti-obesity effects in high-fat induced mouse models. MATERIALS AND METHODS: C57BL/6 mice were randomized into normal control, high-fat diet (HFD), HFD with OLE, and HFD with garcinia groups and administered experimental diets for 12 weeks. Body weight and food intake were measured once per week and obesity-related biomarkers were evaluated in the serum and adipose tissue. RESULTS: OLE significantly suppressed weight gain, food efficiency ratio, visceral fat accumulation, and serum lipid composition in HFD-induced mice. Furthermore, the expression of adipogenesis- and thermogenesis-related molecules was decreased in the OLE-treated group. CONCLUSION: OLE prevents obesity development by regulating the expression of molecules involved in adipogenesis and thermogenesis.


Assuntos
Fármacos Antiobesidade/farmacologia , Olea/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Adipogenia/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/química , Biomarcadores , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Metabolismo dos Lipídeos , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Extratos Vegetais/química , Termogênese/efeitos dos fármacos
20.
Nutrients ; 11(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010163

RESUMO

It is difficult to know if the cause for obesity is the type of sweetener, high fat (HF) content, or the combination of sweetener and fat. The purpose of the present work was to study different types of sweeteners; in particular, steviol glycosides (SG), glucose, fructose, sucrose, brown sugar, honey, SG + sucrose (SV), and sucralose on the functionality of the adipocyte. Male Wistar rats were fed for four months with different sweeteners or sweetener with HF added. Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination of fat and sweetener showed an additive effect on circulating levels of GIP and GLP-1 except for honey, SG, and brown sugar. In adipose tissue, sucrose and sucralose stimulated TLR4, and c-Jun N-terminal (JNK). The combination of HF with sweeteners increased NFκB, with the exception of SG and honey. Honey kept the insulin signaling pathway active and the smallest adipocytes in white (WAT) and brown (BAT) adipose tissue and the highest expression of adiponectin, PPARγ, and UCP-1 in BAT. The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 (BCKDH) and increased branched chain amino acids (BCAA) levels by sucrose and sucralose. Our data suggests that the consumption of particular honey maintained functional adipocytes despite the consumption of a HF diet.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Dieta Hiperlipídica , Açúcares da Dieta/farmacologia , Insulina/sangue , Edulcorantes/farmacologia , Papilas Gustativas/metabolismo , Receptor 4 Toll-Like/metabolismo , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/sangue , Adiponectina/sangue , Tecido Adiposo/citologia , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Mel , Incretinas/sangue , Inflamação/metabolismo , Masculino , Proteínas de Membrana Transportadoras/sangue , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , PPAR gama/sangue , Ratos Wistar , Stevia , Sacarose/análogos & derivados , Sacarose/farmacologia , Paladar , Proteína Desacopladora 1/sangue
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