Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

ObjectivePrevious studies have shown that active brown adipose tissue (BAT) is present in adults and may play important roles in the regulation of energy homeostasis. However, nearly every study has been carried out in patients undergoing scanning for cancer surveillance (CS), whose metabolism and BAT activity may not reflect those of healthy individuals. The objective of this study was to investigate the prevalence and predictors of active BAT in Chinese adults, particularly in healthy individuals.DesignA total of 31 088 consecutive subjects aged ≥18 years who had undergone positron emission tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this study.MethodsWe measured BAT activity via18F-fluorodeoxyglucose PET/CT in subjects who had undergone scanning for either a routine medical checkup (MC) or CS in Shanghai. Then, we investigated the predictors of active BAT, particularly in healthy individuals.ResultsIn both groups, the prevalence of BAT was higher in women than in men. Using a multivariate logistic analysis, we found age, sex, BMI, and high thyroid glucose uptake to be significant predictors of BAT activity in the MC group. Similarly, we found age, sex, and BMI to be significant predictors of BAT activity, but not thyroid high glucose uptake, in the CS group.ConclusionsIn Chinese adults, BAT activity inversely correlates with BMI and thyroid high glucose uptake, which reinforces the central role of brown fat in adult metabolism and provides clues to a potential means for treating the metabolic syndrome.

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The development of insulin resistance in brown adipose tissue may impair the acute cold-induced activation of thermogenesis in genetically obese (ob/ob) mice

Bioscience Reports ◽

10.1007/bf01116891 ◽

1984 ◽

Vol 4 (11) ◽

pp. 933-940 ◽

Cited By ~ 31

Author(s):

Stewart W. Mercer ◽

Paul Trayhurn

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Brown Fat ◽

Acute Cold Exposure ◽

Brown Adipose

Genetically obese (ob/ob) mice develop insulin resistance in brown adipose tissue during the fifth week of life. Prior to this, at 26 days of age, oh/oh mice show a substantial increase in GDP binding to brownadipose-tissue mitochondria during acute cold exposure. When insulin resistance in brown fat develops, by 35 days of age, the increase in GDP binding in response to cold is markedly reduced. Studies with 2-deoxyglucose suggest that insulin resistance in brown adipose tissue could impair thermogenic responsiveness during acute cold exposure by limiting the ability of the tissue to take up glucose.

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mTORC 2 sustains thermogenesis via Akt‐induced glucose uptake and glycolysis in brown adipose tissue

EMBO Molecular Medicine ◽

10.15252/emmm.201505610 ◽

2016 ◽

Vol 8 (3) ◽

pp. 232-246 ◽

Cited By ~ 64

Author(s):

Verena Albert ◽

Kristoffer Svensson ◽

Mitsugu Shimobayashi ◽

Marco Colombi ◽

Sergio Muñoz ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Glucose Uptake ◽

Brown Adipose

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Fatty acid synthesis and generation of glycerol-3-phosphate in brown adipose tissue from rats fed a cafeteria diet

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-052 ◽

2008 ◽

Vol 86 (7) ◽

pp. 416-423 ◽

Cited By ~ 12

Author(s):

Valéria E. Chaves ◽

Danúbia Frasson ◽

Maria E.S. Martins-Santos ◽

Luiz C.C. Navegantes ◽

Victor D. Galban ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Glucose Uptake ◽

Fatty Acid Synthesis ◽

Fatty Acid Content ◽

Acid Synthesis ◽

Cafeteria Diet ◽

Brown Adipose

In vivo fatty acid synthesis and the pathways of glycerol-3-phosphate (G3P) production were investigated in brown adipose tissue (BAT) from rats fed a cafeteria diet for 3 weeks. In spite of BAT activation, the diet promoted an increase in the carcass fatty acid content. Plasma insulin levels were markedly increased in cafeteria diet-fed rats. Two insulin-sensitive processes, in vivo fatty acid synthesis and in vivo glucose uptake (which was used to evaluate G3P generation via glycolysis) were increased in BAT from rats fed the cafeteria diet. Direct glycerol phosphorylation, evaluated by glycerokinase (GyK) activity and incorporation of [U-14C]glycerol into triacylglycerol (TAG)–glycerol, was also markedly increased in BAT from these rats. In contrast, the cafeteria diet induced a marked reduction of BAT glyceroneogenesis, evaluated by phosphoenolpyruvate carboxykinase-C activity and incorporation of [1-14C]pyruvate into TAG–glycerol. BAT denervation resulted in an approximately 50% reduction of GyK activity, but did not significantly affect BAT in vivo fatty acid synthesis, in vivo glucose uptake, or glyceroneogenesis. The data suggest that the supply of G3P for BAT TAG synthesis can be adjusted independently from the sympathetic nervous system and solely by reciprocal changes in the generation of G3P via glycolysis and via glyceroneogenesis, with no participation of direct phosphorylation of glycerol by GyK.

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Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.5.e576 ◽

1986 ◽

Vol 251 (5) ◽

pp. E576-E583 ◽

Cited By ~ 79

Author(s):

L. H. Storlien ◽

D. E. James ◽

K. M. Burleigh ◽

D. J. Chisholm ◽

E. W. Kraegen

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Energy Expenditure ◽

Metabolic Rate ◽

Brown Adipose Tissue ◽

Whole Body ◽

Brown Adipose ◽

Glucose Output ◽

Fat Feeding

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

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