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Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation.

ABSTRACT: Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD displayed an obese phenotype and down-regulated expression of thermogenic regulators including Ucp-1 and Pgc-1α in adipose tissue. Excitingly, NaB add-on treatment abolished these detrimental effects. Moreover, the obesity-induced insulin resistance, inflammation, fatty liver, and intestinal dysfunction were also attenuated by NaB administration. Mechanistically, NaB can promote fat thermogenesis via the increased local sympathetic innervation of adipose tissue, and blocking the β3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis. Our study reveals a potential pharmacological target for NaB to combat obesity and metabolic disorders.

SUBMITTER: Zhu W

PROVIDER: S-EPMC9574364 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis <i>via</i> intro-adipose sympathetic innervation.

Zhu Wanlong W Peng Ke K Zhao Yan Y Xu Changjing C Tao Xuemei X Liu Yuanzhi Y Huang Yilan Y Yang Xuping X

Frontiers in pharmacology 20221003

Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD dis ...[more]

PMID: 36263123

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Project description:Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

Project description:BackgroundExposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis.MethodsPregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p'-DDT and o,p'-DDT) or DDE (p,p'-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated.ResultsWe observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p'-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p'-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p'-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p'-DDE, respectively, compared to control.ConclusionsThese data demonstrate that perinatal exposure to DDTs or p,p'-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT.

Dataset Information

Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation.

Publications

Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis <i>via</i> intro-adipose sympathetic innervation.

Similar Datasets

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