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1.
PLoS Biol ; 20(9): e3001743, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36126044

RESUMO

The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat mass than germ-free (GF) or fully colonized counterparts. We therefore investigated their food intake, digestion efficiency, energy expenditure, and respiratory quotient using a novel isolator-housed metabolic cage system, which allows long-term measurements without contamination risk. This demonstrated that microbiota-released calories are perfectly balanced by decreased food intake in fully colonized versus gnotobiotic OligoMM12 and GF mice fed a standard chow diet, i.e., microbiota-released calories can in fact be well integrated into appetite control. We also observed no significant difference in energy expenditure after normalization by lean mass between the different microbiota groups, suggesting that cumulative small differences in energy balance, or altered energy storage, must underlie fat accumulation in OligoMM12 mice. Consistent with altered energy storage, major differences were observed in the type of respiratory substrates used in metabolism over the circadian cycle: In GF mice, the respiratory exchange ratio (RER) was consistently lower than that of fully colonized mice at all times of day, indicative of more reliance on fat and less on glucose metabolism. Intriguingly, the RER of OligoMM12-colonized gnotobiotic mice phenocopied fully colonized mice during the dark (active/eating) phase but phenocopied GF mice during the light (fasting/resting) phase. Further, OligoMM12-colonized mice showed a GF-like drop in liver glycogen storage during the light phase and both liver and plasma metabolomes of OligoMM12 mice clustered closely with GF mice. This implies the existence of microbiota functions that are required to maintain normal host metabolism during the resting/fasting phase of circadian cycle and which are absent in the OligoMM12 consortium.


Assuntos
Glicogênio Hepático , Microbiota , Animais , Vida Livre de Germes , Glucose , Camundongos , Obesidade/metabolismo
2.
Adipocyte ; 11(1): 588-600, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36082406

RESUMO

Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK-ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Tecido Adiposo/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Obesidade/metabolismo , Transdução de Sinais
3.
Mol Brain ; 15(1): 75, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064426

RESUMO

Fibroblast growth factor 11 (FGF11) is a member of the intracellular fibroblast growth factor family. Here, we report the central role of FGF11 in the regulation of metabolism. Lentiviral injection of Fgf11 shRNA into the arcuate nucleus of the mouse hypothalamus decreased weight gain and fat mass, increased brown adipose tissue thermogenesis, and improved glucose and insulin intolerances under high-fat diet conditions. Fgf11 was expressed in the NPY-expressing neurons, and Fgf11 knockdown considerably decreased Npy expression and projection, leading to increased expression of tyrosine hydroxylase in the paraventricular nucleus. Mechanistically, FGF11 regulated Npy gene expression through the glycogen synthase kinase 3-cAMP response element-binding protein pathway. Our study defines the physiological significance of hypothalamic FGF11 in the regulation of metabolism in response to overnutrition such as high-fat diet.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Hipotálamo , Neuropeptídeo Y , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Dieta Hiperlipídica , Fatores de Crescimento de Fibroblastos/genética , Hipotálamo/metabolismo , Camundongos , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/farmacologia , Obesidade/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo
4.
Nutrients ; 14(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36079890

RESUMO

Phycobiliproteins (derived from Arthrospira platensis) bioactive peptide extracts (PPE) possess multiple pharmacological effects in the mitigation of human metabolic disorders. The role of PPE in the treatment of diet-induced obesity and the understanding of the underlying mechanism between the gut microbiome and metabolic blood circulation for obese patients remains poorly understood. In this study, we showed that PPE attenuated obesity by reducing body weight, and ameliorated glucose and lipid indexes in serum. In particular, PPE is postulated to mitigate liver steatosis and insulin resistance. On the other hand, dietary treatment with PPE was found to "reconfigure" the gut microbiota in the way that the abundances were elevated for Akkermansia_muciniphila, beneficial Lactobacillus and Romboutsia, SCFA-producing species Faecalibacterium prausnitzii, Lachnospiraceae_bacterium, Clostridiales_bacterium, probiotics Clostridium sp., Enterococcus faecium, and Lactobacillus_johnsonii, while the abundance of Firmicutes was reduced and that of Bacteroidetes was increased to reverse the imbalance of Firmicutes/Bacteroidetes ratio. Finally, the metabolomics of circulating serum using UHPLC-MS/MS illustrated that PPE supplementation indeed promoted lipid metabolism in obese rats. As summary, it was seen that PPE reprogrammed the cell metabolism to prevent the aggravation of obesity. Our findings strongly support that PPE can be regarded as a potential therapeutic dietary supplement for obesity.


Assuntos
Microbioma Gastrointestinal , Obesidade , Ficobiliproteínas , Animais , Dieta Hiperlipídica , Humanos , Fígado/metabolismo , Obesidade/metabolismo , Obesidade/terapia , Peptídeos/farmacologia , Ficobiliproteínas/farmacologia , Ratos , Espectrometria de Massas em Tandem
5.
Front Endocrinol (Lausanne) ; 13: 938527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111301

RESUMO

Objectives: N-linoleyltyrosine (NITyr) showed mild effects in preclinical studies. The research discussed the effect of NITyr on a high-fat diet (HFD) induced obese (DIO) mice, and preliminarily explored its mechanism. Methods: The DIO mice were established by feeding an HFD for 12 weeks and subsequently administrated orally with NITyr (30, 60 and 100 mg/kg) for four weeks. The indexes of serum and liver samples were determined by ELISA kit. The pathological status of adipose and liver were detected by HE staining. The factors related to energy and lipid metabolism were measured via western blot. Results: NITyr at 60 and 100 mg/kg/day suppressed the weight gain without affecting water and food intake. Accordingly, NITyr reduced adipose weight and the area of individual adipocytes and increased the number of adipocytes. Moreover, NITyr didn't affect the appetite-related indexes such as ghrelin, peptide YY and brain-derived neurotrophic factor. Besides, NITyr didn't affect other organ coefficients except for the liver. Correspondingly, NITyr reduced alanine aminotransferase and aspartate aminotransferase levels, yet didn't influence IL-1ß and TNF-α levels, and the liver injury. The levels of triacylglycerol (TG), total cholesterol (TC), glucose, insulin, adiponectin and leptin in serum were assessed to evaluate the effect of NITyr on glucose and lipid metabolism. NITyr decreased the levels of TG, TC and glucose, and didn't affect insulin, adiponectin and leptin levels. Meanwhile, NITyr up-regulated p-AMPK and the cannabinoid receptor 2 (CB2) expressions, and down-regulated PPAR, FAS and cannabinoid receptor 1 (CB1) expressions.Overall, NITyr suppressed lipid accumulation via improving lipid and glucose metabolism involving CB1 and CB2 receptors.


Assuntos
Dieta Hiperlipídica , Insulinas , Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina , Alanina Transaminase , Animais , Aspartato Aminotransferases , Fator Neurotrófico Derivado do Encéfalo , Colesterol , Dieta Hiperlipídica/efeitos adversos , Grelina , Glucose , Leptina , Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Peptídeo YY , Receptores Ativados por Proliferador de Peroxissomo , Receptores de Canabinoides , Triglicerídeos , Fator de Necrose Tumoral alfa , Tirosina/análogos & derivados , Água
6.
Front Immunol ; 13: 977485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119080

RESUMO

Adipose tissue macrophage (ATM) has been appreciated for its critical contribution to obesity-associated metabolic diseases in recent years. Here, we discuss the regulation of ATM on both metabolic homeostatsis and dysfunction. In particular, the macrophage polarization and recruitment as well as the crosstalk between ATM and adipocyte in thermogenesis, obesity, insulin resistance and adipose tissue fibrosis have been reviewed. A better understanding of how ATM regulates adipose tissue remodeling may provide novel therapeutic strategies against obesity and associated metabolic diseases.


Assuntos
Inflamação , Resistência à Insulina , Tecido Adiposo/metabolismo , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo
7.
Zhongguo Zhen Jiu ; 42(9): 966-70, 2022 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-36075590

RESUMO

OBJECTIVE: To assess the efficacy of the combined treatment with electroacupuncture (EA) and intradermal needling on simple obesity and explore its underlying effect mechanism. METHODS: A total number of 116 patients with simple obesity were randomized into an observation group (58 cases, 3 cases dropped off and 2 cases removed) and a control group (58 cases, 4 cases dropped off and 1 cases removed). Patients in the control group received EA at Zhongwan (CV 12), Quchi (LI 11), Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21), etc., for 30 min each time. On the base of the intervention as the control group, the patients in the observation group received the intradermal needling at Tianshu (ST 25), Daheng (SP 15), Zusanli (ST 36), Shangjuxu (ST 37), Quchi (LI 11), Pishu (BL 20) and Weishu (BL 21). In each group, the intervention was given once every two days, 3 times a week, consecutively for 3 months. Before and after treatment, the obesity indexes (body mass [BW], body mass index [BMI], body fat percentage [F%], adiposity [A] and waist circumference [WC]), the serum intestinal lymphatic function-related factors (vascular endothelial growth factor C [VEGF-C], delta-like ligand 4 [DLL4], adrenomedullin [ADM]), blood lipid (total cholesterol [TC], triglyceride [TG] and low density lipoprotein-cholesterol [LDL-C]), and fasting plasma glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were observed in the patients of both groups; and the efficacy was assessed. RESULTS: The effective rate was 88.7% (47/53) in the observation group, higher than 71.7% (38/53) in the control group (P<0.05). After treatment, except FPG in the control group, BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, as well as TC, TG, LDL-C, FBG, FINS and HOMA-IR were all reduced compared with those before treatment in both groups (P<0.05). The reduction ranges of BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, and TC, LDL-C, FINS and HOMA-IR in the observation group were all larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with intradermal needling can reduce body weight and lipid, and improve insulin resistance in treatment of simple obesity, which is achieved probably through inhibiting lymphangiogenesis and promoting lymphatic endothelial permeability.


Assuntos
Eletroacupuntura , Resistência à Insulina , Obesidade Mórbida , Pontos de Acupuntura , Glicemia/metabolismo , LDL-Colesterol , Humanos , Intestinos , Lipídeos , Linfócitos , Obesidade/metabolismo , Obesidade/terapia , Triglicerídeos , Fator C de Crescimento do Endotélio Vascular
8.
BMC Genomics ; 23(1): 660, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36117155

RESUMO

BACKGROUND: Brown adipose tissue (BAT) is considered as a primary location of adaptive thermogenesis and the thermogenic activities of brown adipocytes are also connected to generating heat and counteracting obesity. Recent studies revealed that BAT could secrete certain batokines-like factors especially small extracellular vesicles (sEVs), which contributed to the systemic consequences of BAT activities. As a newly emerging class of mediators, some long non-coding RNAs (lncRNAs) have exhibited metabolic regulatory effects in adipocyte development. However, besides the well-studied lncRNAs, the lncRNAs carried by sEVs derived from brown adipose tissue (sEV-BAT) have not been identified yet.  RESULTS: In this study, we demonstrated that sEV-BAT could induce beige adipocyte differentiation both in ASCs and 3T3-L1 cells, while sEV-WAT had no corresponding effects. The lncRNA microarray assay on sEV-WAT and sEV-BAT revealed a total of 563 types of known lncRNAs were identified to be differentially expressed, among which 232 lncRNAs were upregulated and 331 lncRNAs were downregulated in sEV-BAT. Three novel candidates (AK029592, humanlincRNA1030 and ENSMUST00000152284) were selected for further validation. LncRNA-mRNA network analysis revealed candidate lncRNAs were largely embedded in cellular metabolic pathways. During adipogenic and thermogenic phenotype differentiation in ASCs and 3T3-L1 cells, only the expressions of AK029592 were upregulated. The three lncRNAs were all relatively enriched in brown adipose tissues and brown adipocytes. In different adipocytes, sEV and adipose tissue, the expression of AK029592 and ENSMUST00000152284 were remarkably decreased in obese mice compared to lean mice, while obesity state could not change the expression of humanlincRNA1030. CONCLUSION: Collectively, our profiling study provided a comprehensive catalog for the study of lncRNAs specifically carried by sEV-BAT and indicated the potential regulatory role of certain sEV-BAT lncRNAs in thermogenesis.


Assuntos
Vesículas Extracelulares , RNA Longo não Codificante , Tecido Adiposo Marrom/metabolismo , Animais , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Camundongos , Obesidade/genética , Obesidade/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Termogênese/genética
9.
PLoS One ; 17(9): e0270306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112580

RESUMO

Obesity is a leading global health problem contributing to various chronic diseases, including type II diabetes mellitus (T2DM). The aim of this study was to investigate whether blueberries, yoghurt, and their respective bioactive components, Cyanidin-3-O-ß-glucoside (C3G) and peptides alone or in combinations, alter the expression of genes related to glucose metabolism in skeletal muscles from diet-induced obese mice. In extensor digitorum longus (EDL), yoghurt up-regulated the expression of activation of 5'adenosine monophosphate-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3 kinase (PI3K) and glucose transporter 4 (GLUT4), and down-regulated the expression of angiotensin II receptor type 1 (AGTR-1). The combination of blueberries and yoghurt down-regulated the mRNA expression of AGTR-1 and Forkhead box protein O1 (FoxO1) in the EDL. Whereas the combination of C3G and peptides down-regulated AGTR-1 and up-regulated GLUT4 mRNA expression in the EDL. In the soleus, blueberries and yoghurt alone, and their combination down-regulated AGTR-1 and up-regulated GLUT4 mRNA expression. In summary blueberries and yoghurt, regulated multiple genes associated with glucose metabolism in skeletal muscles, and therefore may play a role in the management and prevention of T2DM.


Assuntos
Mirtilos Azuis (Planta) , Diabetes Mellitus Tipo 2 , Proteínas Quinases Ativadas por AMP/metabolismo , Monofosfato de Adenosina/metabolismo , Animais , Antocianinas/metabolismo , Antocianinas/farmacologia , Mirtilos Azuis (Planta)/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Proteína Forkhead Box O1/metabolismo , Expressão Gênica , Glucose/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Camundongos Obesos , Músculo Esquelético/metabolismo , Obesidade/genética , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis/metabolismo , RNA Mensageiro/metabolismo , Receptores de Angiotensina/metabolismo , Iogurte
10.
Iran J Med Sci ; 47(5): 422-432, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36117580

RESUMO

Background: The rising prevalence of obesity, as well as its detrimental effects on the brain, has drawn attention to specific dietary patterns. This study aimed to examine the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) pattern on anthropometric parameters, hunger hormones, and brain structures in overweight and obese women. Methods: This randomized trial was conducted in Shiraz between October 2018 and March 2019. We analyzed 37 healthy women with a mean age of 48±5.38 years and a Body Mass Index (BMI) of 32±0.69 Kg/m2. Participants were randomly allocated to a hypocaloric modified MIND diet or a hypocaloric control diet. Differences in anthropometric, laboratory analysis, and brain structure were determined at baseline and three-month follow-up. Data were analyzed using SPSS 22.0. Independent and paired sample t test were used to determine between and within differences. We also used mixed-model ANOVA to compare the mean differences between two-factor groups. Results: A more significant weight reduction (P<0.0001), BMI (P<0.0001), percentage of body fat (P=0.03), waist circumference (P=0.01), and Leptin concentration (P=0.03) were found in the MIND diet group. The results also showed a significant increase in Ghrelin (P=0.002) and GLP-1 (P=0.01) levels in the MIND diet group. The findings revealed no differences in the whole and regional brain structures between the two groups. Conclusion: For the first time, this study showed that the MIND diet intervention could improve the devastating effect of obesity on metabolic profiles and anthropometric parameters. However, we could not find its effect on brain structures.Trial registration number: IRCT20190427043387N1.A preprint of this study was published at https://www.medrxiv.org/content/10.1101/2020.06.28.20142018v1.


Assuntos
Leptina , Sobrepeso , Adulto , Encéfalo/metabolismo , Feminino , Grelina , Peptídeo 1 Semelhante ao Glucagon , Humanos , Fome , Leptina/metabolismo , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/metabolismo , Sobrepeso/terapia
11.
Nat Commun ; 13(1): 5208, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064857

RESUMO

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1ß was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.


Assuntos
Resistência à Insulina , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Humanos , Inflamação/patologia , Resistência à Insulina/fisiologia , Ácido Láctico/metabolismo , Macrófagos/metabolismo , Camundongos , Obesidade/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prolil Hidroxilases/metabolismo
12.
Carbohydr Polym ; 296: 119903, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087969

RESUMO

Obesity is nowadays a serious public health issue. Neoagarotetraose (NA4) is a marine oligosaccharide produced by the enzymatic hydrolysis of agar by ß-agarase. The present study is aimed to determine the effect of NA4 on high-fat diet (HFD)-induced obesity in mice and uncover the regulating role of gut microbiota and microbial metabolites. The results showed that the intervention of NA4 significantly reduced the body weight gain, insulin resistance, hepatic adipose accumulation, serum lipid levels, oxidative damages, and inflammation responses in HFD-induced obese mice. NA4 also promoted lipolysis and browning of white adipose tissue, inhibit lipogenesis, and protect the integrity of gut barrier. Moreover, NA4 restructured the altered gut microbiota and enhanced the content of short-chain fatty acids (SCFAs) in the feces with compared with the HFD group. Cumulatively, these findings suggest that NA4 can relieve obesity by stimulating white adipose tissue browning, regulating intestinal flora, and promoting microbial metabolism.


Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Adipócitos Brancos/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Galactosídeos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Oligossacarídeos/farmacologia
13.
Mediators Inflamm ; 2022: 7853482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065376

RESUMO

The adipose tissue NLRP3 inflammasome has recently emerged as a contributor to obesity-related metabolic inflammation. Recent studies have demonstrated that the activation of the NLRP3 inflammasome cleaves gasdermin D (GSDMD) and induces pyroptosis, a proinflammatory programmed cell death. However, whether GSDMD is involved in the regulation of adipose tissue function and the development of obesity-induced metabolic disease remains unknown. The aim of the present study was to investigate the role of GSDMD in adipose tissue inflammation as well as whole-body metabolism using GSDMD-deficient mice fed a high-fat diet (HFD) for 30 weeks. The effects of GSDMD deficiency on adipose tissue, liver, and isolated macrophages from wild-type (WT) and GSDMD knockout (KO) mice were examined. In addition, 3T3-L1 cells were used to examine the expression of GSDMD during adipogenesis. The results demonstrate that although HFD-induced inflammation was partly ameliorated in isolated macrophages and liver, adipose tissue remained unaffected by GSDMD deficiency. Compared with the WT HFD mice, GSDMD KO HFD mice exhibited a mild increase in HFD-induced glucose intolerance with increased systemic and adipose tissue IL-1ß levels. Interestingly, GSDMD deficiency caused accumulation of fat mass when challenged with HFD, partly by suppressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ). The expression of GSDMD mRNA and protein was dramatically suppressed during adipocyte differentiation and was inversely correlated with PPARγ expression. Together, these findings indicate that GSDMD is not a prerequisite for HFD-induced adipose tissue inflammation and suggest a noncanonical function of GSDMD in regulation of fat mass through PPARγ.


Assuntos
Tecido Adiposo , Dieta Hiperlipídica , Intolerância à Glucose , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Obesidade/metabolismo , PPAR gama/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros/genética
14.
Nutrients ; 14(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36079733

RESUMO

Obesity is frequently associated with dysregulated lipid metabolism and lipotoxicity. Inonotus hispidus (Bull.: Fr.) P. Karst (IH) is an edible and medicinal parasitic mushroom. In this study, after a systematic analysis of its nutritional ingredients, the regulatory effects of IH on lipid metabolism were investigated in mice fed a high-fat diet (HFD). In HFD-fed mice, IH reversed the pathological state of the liver and the three types of fat and significantly decreased the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and leptin (LEP) and increased the level of high-density liptein cholesterol (HDL-C) in serum. Meanwhile, IH ameliorated liver damage by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) levels in the liver and serum. Compared with HFD-fed mice, IH significantly modulated the gut microbiota, changed the relative abundances of microflora at different taxonomic levels, and regulated lipid levels. The results showed that 30 differential lipids were found. Results from Western blotting confirmed that IH regulated the nuclear factor erythroid-2 related factor 2 (Nrf2)/nuclear factor-kappa B (NF-κB) signaling pathway and oxidative stress. This study aimed to provide experimental evidence for the applicability of IH in obesity treatment.


Assuntos
Dieta Hiperlipídica , Hiperlipidemias , Animais , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/metabolismo , Inflamação/metabolismo , Inonotus , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Obesidade/metabolismo , Estresse Oxidativo , Transdução de Sinais
15.
Nutrients ; 14(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36079789

RESUMO

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Sarcopenia , Inibidores do Transportador 2 de Sódio-Glicose , Aminoácidos , Animais , Dieta com Restrição de Carboidratos , Masculino , Camundongos , Obesidade/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Sorbitol/análogos & derivados
16.
Nutrients ; 14(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36079828

RESUMO

Nowadays, slimming diet methodology works within a reduction of body mass using a decrease of dietary energy intake. However, there is no suitable method for understanding the dynamic process of body mass metabolic transformation over time. In the present paper, we have developed a biomathematic model to explain the temporal trend of body mass and its variations of people who have undergone a change in their diet using the solving equation of the model. Data relating to sex, age, body mass, and BMI were collected, and the compartmental model used to interpret the body mass trends was constructed by assuming that the mass results from the sum of the metabolic processes: catabolic, anabolic, distributive. The validation of the model was carried out by variance analysis both on the total and individual data sets. The results confirm that the trend of body mass and its variations over time depends on metabolic rates. These are specific to each individual and characterize the distribution of nutritional molecules in the various body districts and the processes catabolic, anabolic, distributive. Body mass and its variations are justified by the metabolic transformations of the nutritional quantities. This would explain why energetically equal diets can correspond to people of different body mass and that energy-different diets can correspond to people of body mass at all similar.


Assuntos
Dieta , Obesidade , Índice de Massa Corporal , Ingestão de Alimentos , Ingestão de Energia , Humanos , Modelos Teóricos , Obesidade/metabolismo
17.
Nutrients ; 14(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36079831

RESUMO

Adolescence is a period of intense growth and endocrine changes, and obesity and insulin-resistance processes during this period have lately been rising. Selenium (Se) homeostasis is related to lipid metabolism depending on the form and dose of Se. This study tests the actions of low-dose selenite and Se nanoparticles (SeNPs) on white (WAT) and brown adipose tissue (BAT) deposition, insulin secretion, and GPx1, IRS-1 and FOXO3a expression in the WAT of adolescent rats as regards oxidative stress, adipocyte length and adipokine secretion. Four groups of male adolescent rats were treated: control (C), low selenite supplementation (S), low SeNP supplementation (NS) and moderate SeNP supplementation (NSS). Supplementation was received orally through water intake; NS and NSS rats received two- and tenfold more Se than C animals, respectively. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. For the first time in vivo, it was demonstrated that low selenite supplementation contributed to increased adipogenesis via the insulin signaling pathway and LCN2 modulation, while low SeNP administration prevented fat depots in WAT via the decrease in insulin signaling and FOXO3a autophagy in WAT, lowering inflammation. These effects were independent of GPx1 expression or activity in WAT. These findings provide data for dietary approaches to prevent obesity and/or anorexia during adolescence. These findings may be relevant to future studies looking at a nutritional approach aimed at pre-venting obesity and/or anorexia in adolescence.


Assuntos
Nanopartículas , Selênio , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Anorexia/metabolismo , Dieta Hiperlipídica , Suplementos Nutricionais , Insulina/metabolismo , Secreção de Insulina , Masculino , Obesidade/metabolismo , Ratos , Ácido Selenioso/metabolismo , Selênio/metabolismo , Selênio/farmacologia
18.
Sci Rep ; 12(1): 14840, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050326

RESUMO

Understanding the interactions between diet, obesity, and diabetes is important to tease out mechanisms in painful pathology. Western diet is rich in fats, producing high amounts of circulating bioactive metabolites. However, no research has assessed how a high-fat diet (HFD) alone may sensitize an individual to non-painful stimuli in the absence of obesity or diabetic pathology. To investigate this, we tested the ability of a HFD to stimulate diet-induced hyperalgesic priming, or diet sensitization in male and female mice. Our results revealed that 8 weeks of HFD did not alter baseline pain sensitivity, but both male and female HFD-fed animals exhibited robust mechanical allodynia when exposed to a subthreshold dose of intraplantar Prostaglandin E2 (PGE2) compared to mice on chow diet. Furthermore, calcium imaging in isolated primary sensory neurons of both sexes revealed HFD induced an increased percentage of capsaicin-responsive neurons compared to their chow counterparts. Immunohistochemistry (IHC) showed a HFD-induced upregulation of ATF3, a neuronal marker of injury, in lumbar dorsal root ganglia (DRG). This suggests that a HFD induces allodynia in the absence of a pre-existing condition or injury via dietary components. With this new understanding of how a HFD can contribute to the onset of pain, we can understand the dissociation behind the comorbidities associated with obesity and diabetes to develop pharmacological interventions to treat them more efficiently.


Assuntos
Diabetes Mellitus , Dieta Hiperlipídica , Animais , Diabetes Mellitus/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Dor/metabolismo
19.
Sci Rep ; 12(1): 14895, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050341

RESUMO

Transplacental docosahexaenoic-acid (DHA) supply for fetal development is regulated by placental DHA-lipid metabolism. Both maternal diabetes and obesity are linked to possible decreased fetal circulating DHA and increased placental DHA-lipids. Since myo-inositol is a promising intervention for gestational diabetes (GDM), we aimed to determine whether myo-inositol could rectify perturbations in placental DHA metabolism associated with maternal increasing glycemia and obesity and examine links with birthweight. Term placental villous explants from 17 women representing a range of BMIs and mid-gestational glycemia, were incubated with 13C-labeled-DHA for 48 h, in 0.3 µmol/L (control) or 60 µmol/L myo-inositol. Individual newly synthesized 13C-DHA-labeled lipid species were quantified by liquid-chromatography-mass-spectrometry. Compared with controls, incubation with myo-inositol decreased most 13C-DHA-lipids in placental explants from women with higher BMI or higher glycemia, but increased 13C-DHA-lipids with normal BMI or lower glycemia. Myo-inositol also increased 13C-DHA-labeled lipids in cases of lower birthweight centile, but induced decreases at higher centiles. Myo-inositol therefore lowered DHA-lipids in placenta with high basal placental DHA-lipid production (higher BMI and glycemia) but increased DHA-lipids where basal processing capacity is low. Myo-inositol thus moderates placental DHA metabolism towards a physiological mean which may in turn moderate birthweight.


Assuntos
Diabetes Gestacional , Placenta , Peso ao Nascer , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Gestacional/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Feminino , Humanos , Inositol/metabolismo , Obesidade/metabolismo , Placenta/metabolismo , Gravidez
20.
An Acad Bras Cienc ; 94(suppl 3): e20201066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074424

RESUMO

We investigated the effect of dietary supplementation with kinkan orange on growth, adiposity, metabolic parameters, and oxidative stress in rats with diet-induced hypercholesterolemia. Female Wistar rats (6-8 weeks) were fed a AIN-93M diet (Control); AIN-93M diet containing 5% kinkan orange (CTkinkan); Hypercholesterolemic diet, containing 1% cholesterol and 25% fat (Hyper); or Hypercholesterolemic diet containing 5% kinkan orange (Hyperkinkan). Hypercholesterolemic diet increased body weight, adiposity, serum alanine transaminase (ALT), creatinine, cholesterol and triglycerides, hepatic total lipids, cholesterol, and triglycerides, and hepatic oxidative stress. Supplementation with kinkan reduced the serum and hepatic lipid content, decreased serum ALT, besides improving the antioxidant status in liver tissue of hypercholesterolemic animals. Moreover, HDL-cholesterol increased in both groups supplemented with kinkan orange (CTkinkan and Hyperkinkan). Our data suggest that diet supplementation with kinkan orange may consist of a valid strategy to prevent or reduce dyslipidemia and oxidative stress in hypercholesterolemic rats.


Assuntos
Citrus sinensis , Dislipidemias , Alanina Transaminase , Animais , Colesterol , Citrus sinensis/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Feminino , Fígado , Obesidade/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Triglicerídeos
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