Glucose Metabolism and the Response to Insulin by Human Adipose Tissue in Spontaneous and Experimental Obesity

Salans, Lester B.; Bray, George A.; Cushman, Samuel W.; Danforth, Elliot; Glennon, Joseph A.; Horton, Edward S.; Sims, Ethan A. H.

doi:10.1172/jci107625

Cited by 88 publications

(33 citation statements)

References 24 publications

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“…An increase in size and hypoxia, along with a reduced membrane translocation of GLUT4 and an increased expression of perilipin, was observed in VAT adipocytes isolated from the HFD rabbits. Indeed, not only the total mass of AT conveys a metabolic risk, but the size of adipocytes is also important, being positively associated with insulin resistance (Jacobsson & Smith 1972, Salans et al 1974. Findings regarding the normalization of insulin resistance after weight loss, associated with a reduction in adipose cell size (Salans et al 1968), further corroborate this concept.…”

Section: Discussionmentioning

confidence: 96%

FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS

Maneschi¹,

Vignozzi²,

Morelli³

et al. 2013

Journal of Endocrinology

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Insulin resistance is the putative key underlying mechanism linking adipose tissue (AT) dysfunction with liver inflammation and steatosis in metabolic syndrome (MetS). We have recently demonstrated that the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA) ameliorates insulin resistance and the metabolic profile with a marked reduction in the amount of visceral AT (VAT) in a high-fat diet (HFD)-induced rabbit model of MetS. These effects were mediated by the activation of FXR, since treatment with the selective TGR5 agonist INT-777 was not able to ameliorate the metabolic parameters evaluated. Herein, we report the effects of in vivo OCA dosing on the liver, the VAT, and the adipogenic capacity of VAT preadipocytes (rPADs) isolated from rabbits on a HFD compared with those on a control diet. VAT and liver were studied by immunohistochemistry, Western blot analysis, and RT-PCR. rPADs were exposed to a differentiating mixture to evaluate adipogenesis. Adipocyte size, hypoxia, and the expression of perilipin and cytosolic insulin-regulated glucose transporter GLUT4 (SLC2A4) were significantly increased in VAT isolated from the HFD rabbits, and normalized by OCA. The expression of steatosis and inflammation markers was increased in the liver of the HFD rabbits and normalized by OCA. rPADs isolated from the HFD rabbits were less sensitive to insulin, as demonstrated by the decreased insulin-induced glucose uptake, triglyceride synthesis, and adipogenic capacity, as well as by the impaired fusion of lipid droplets. OCA treatment preserved all the aforementioned metabolic functions. In conclusion, OCA dosing in a MetS rabbit model ameliorates liver and VAT functions. This could reflect the ability of OCA to restore insulin sensitivity in AT unable to finalize its storage function, counteracting MetS-induced metabolic alterations and pathological AT deposition.

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Section: Discussionmentioning

confidence: 96%

FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS

Maneschi¹,

Vignozzi²,

Morelli³

et al. 2013

Journal of Endocrinology

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“…Again, this has been recognised for many years in both humans [1,6,31,32] and rodents [33], usually by comparing cells from lean and obese individuals. Even within an individual, however, smaller cells are more insulin-sensitive than are larger cells [34].…”

Section: Discussionmentioning

confidence: 99%

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

et al. 2009

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Aims/hypothesis Previous studies have shown relationships between fatty acid ratios in adipose tissue triacylglycerol (TG), adipocyte size and measures of insulin sensitivity. We hypothesised that variations in adipose tissue de novo lipogenesis (DNL) in relation to adiposity might explain some of these observations. Methods In a cross-sectional study, subcutaneous abdominal adipose tissue biopsies from 59 people were examined in relation to fasting and post-glucose insulin sensitivity. Adipocyte size, TG fatty acid composition and mRNA expression of lipogenic genes were determined. Results We found strong positive relationships between adipose tissue TG content of the fatty acids myristic acid (14:0) and stearic acid (18:0) with insulin sensitivity (HOMA model) (p<0.01 for each), and inverse relationships with adipocyte size (p<0.01, p<0.05, respectively).

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“…A major site of insulin action for carbohydrate utilization is the liver (Felig and Wahren, 1971;Wahren and Felig, 1974); another site may be adipose tissue, as shown by the fact that isocaloric high carbohydrate diets enhance the effects of insulin on glucose metabolism in human adipose tissue (Salans et al, 1974). It therefore seems reasonable to suppose that increased sensitivity to endogenous insulin during overfeeding with carbohydrate selectively accelerates the rate of esterification and FFA utilization in human adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Obesity in man is experimentally induced by an excess caloric intake (Salans et al, 1974). However, the mechanism whereby human adipose tissue accumulates its triglyceride content as the cells become enlarged has not been precisely defined.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Hypercaloric High Carbohydrate Diet on Adipose Tissue Metabolism in Man

Chinayon

Goldbrick

1978

Aust J Exp Biol Med

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Summary. The effects of a hypercaloric high carbohydrate diet on lipolysis and esterification were studied in biopsy samples of adipose tissue obtained from 5 healthy subjeets. Overfeeding with carbohydrate enhanced the rate of esterification of free fatty acids (FFA) without any alteration in the rate of lipolysis. The release of FFA from adipose tissue was inhibited. These observations indicate that the utilization of glucose and FFA by adipose tissue for the synthesis of triglycerides was facilitated during weight gain on a high carbohydrate diet.

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Glucose Metabolism and the Response to Insulin by Human Adipose Tissue in Spontaneous and Experimental Obesity

Cited by 88 publications

References 24 publications

FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS

FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

Effects of a Hypercaloric High Carbohydrate Diet on Adipose Tissue Metabolism in Man

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