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Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet.

ABSTRACT: Interscapular brown adipose tissue (BAT) has the capability to take up glucose from the circulation. Despite the important role of BAT in the control of glucose homeostasis, the metabolic fate and function of glucose in BAT remain elusive as there is clear dissociation between glucose uptake and BAT thermogenesis. Interestingly, intracellular glycolysis and lactate production appear to be required for glucose uptake by BAT. Here, we specifically examine whether activation of lactate receptors in BAT plays a key role in regulating glucose homeostasis in mice fed a high-fat diet (HFD). When C57BL/6J mice are given HFD for 5 weeks at 28°C, male, but not female, mice gain body weight and develop hyperglycemia. Importantly, high-fat feeding upregulates expression of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in female C57BL/6J mice, whereas male C57BL/6J mice show reduced HCAR1 expression in BAT. Treatment with the HCAR1 agonist lowers systemic glucose levels in male DIO mice. This reduction is associated with increased glucose uptake in BAT. Therefore, our results suggest that HCAR1 in BAT may contribute to the development of hyperglycemia in male C57BL/6J DIO mice.

SUBMITTER: Kwon E

PROVIDER: S-EPMC6992197 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet.

Kwon Eunjin E Yoo Taesik T Joung Hye-Young HY Jo Young-Hwan YH

PloS one 20200130 1

Interscapular brown adipose tissue (BAT) has the capability to take up glucose from the circulation. Despite the important role of BAT in the control of glucose homeostasis, the metabolic fate and function of glucose in BAT remain elusive as there is clear dissociation between glucose uptake and BAT thermogenesis. Interestingly, intracellular glycolysis and lactate production appear to be required for glucose uptake by BAT. Here, we specifically examine whether activation of lactate receptors in ...[more]

PMID: 31999787

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Project description:BackgroundHexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear.ObjectivesWe investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD).MethodsMale C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue.ResultsIn HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice.ConclusionsOur findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity.CitationYanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect 122:277-283; http://dx.doi.org/10.1289/ehp.1307421.

Project description:BackgroundCombined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated.MethodsFemale mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring.ResultsHFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator-activated receptor-γ co-activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring.ConclusionsLeucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

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Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet.

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Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet.

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