Inhibition of the CD36 receptor reduces visceral fat accumulation and improves insulin resistance in obese mice carrying the BDNF-Val66Metvariant

High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels was explored in diet- and glucocorticoid-induced models of insulin resistance. In the diet-induced model, lean and fa/fa Zucker rats were fed either normal or high-fat (HF) chow over 4 wk. Fat distribution, IMCL content in the tibialis anterior (TA) muscle (IMCLTA), and whole body insulin resistance were measured before and after the 4-wk period. The HF diet-induced increase in IMCLTA was strongly correlated with visceral fat accumulation and greater glucose intolerance in both groups. The increase in IMCLTA to visceral fat accumulation was threefold greater for fa/fa rats. In the glucocorticoid-induced model, insulin sensitivity was impaired with dexamethasone. In vivo adiposity and IMCLTA content measurements were combined with ex vivo analysis of plasma and muscle tissue. Dexamethasone treatment had minimal effects on visceral fat accumulation while increasing IMCLTA levels ∼30% ( P < 0.05) compared with controls. Dexamethasone increased plasma glucose by twofold and increased the saturated fatty acid content of plasma lipids [fatty acid (CH2) n/ωCH3 ratio +15%, P < 0.05]. The lipid composition of the TA muscle was unchanged by dexamethasone treatment, indicating that the relative increase in IMCLTA observed in vivo resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL accumulation in the context of dietary manipulations; however, a “causal” relationship still remains to be determined. Dexamethasone-induced insulin resistance likely operates under a different mechanism, i.e., independently of visceral adiposity.

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Visceral Fat Accumulation Is Related to Impaired Pancreatic Blood Perfusion and Beta-Cell Dysfunction in Obese Women

Annals of Nutrition and Metabolism ◽

10.1159/000519251 ◽

2021 ◽

pp. 1-6

Author(s):

Radka Szotkowská ◽

Jan Gojda ◽

Andrea Plíhalová ◽

Jiří Weichet ◽

Jana Potočková ◽

...

Keyword(s):

Insulin Resistance ◽

Beta Cell ◽

Visceral Fat ◽

Blood Perfusion ◽

Beta Cell Dysfunction ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Cell Dysfunction ◽

Fasting Glycemia ◽

Pancreatic Perfusion

Aims/Hypothesis: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. Methods: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2–L5 vertebrae). Results: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = −0.434, p = 0.017), WHR (r = −0.411, p = 0.024), and VAT (r = −0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = −0.401, p = 0.028) and HOMA-IR (r = −0.376, p = 0.041). Discussion/Conclusion: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

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Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

Journal of the Endocrine Society ◽

10.1210/js.2019-00052 ◽

2019 ◽

Vol 3 (7) ◽

pp. 1409-1416 ◽

Cited By ~ 7

Author(s):

Satoshi Kadowaki ◽

Yoshifumi Tamura ◽

Yuki Someya ◽

Kageumi Takeno ◽

Hideyoshi Kaga ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Fatty Liver ◽

Visceral Fat ◽

Visceral Fat Area ◽

Japanese Men ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Intrahepatic Lipid

Abstract Context Asians have a high prevalence of insulin resistance, even in the nonobese state. Whereas both visceral fat accumulation (VFA) and fatty liver (FL) have been shown to be associated with insulin resistance, it is still unclear which is a better marker to predict insulin resistance in nonobese Asians. Objective The aim of this study was to investigate the relation between VFA or FL and insulin resistance in nondiabetic nonobese Japanese men who do not have diabetes. Design and Participants We studied 87 nonobese (body mass index <25 kg/m2) Japanese men without diabetes. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity in adipose tissue, muscle, and liver. Intrahepatic lipid and abdominal visceral fat area were measured by 1H-magnetic resonance spectroscopy and MRI, respectively. Subjects were divided into four groups based on the presence or absence of VFA (visceral fat area ≥100 cm2) and FL (intrahepatic lipid ≥ 5%): control (non-VFA, non-FL; n = 54), VFA only (n = 18), FL only (n = 7), and VFA plus FL (n = 8). Results Subjects in the FL only and VFA plus FL groups had insulin resistance in adipose tissue and muscle, as well as relatively lower hepatic insulin sensitivity. The specific insulin sensitivities in these organs were comparable in the VFA only and control groups. Conclusions In nonobese Japanese men without diabetes, subjects with FL only or VFA plus FL but not VFA only had insulin resistance, suggesting that FL may be a more useful clinical marker than VFA to predict insulin resistance in nonobese Japanese men without diabetes.

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Visceral fat and insulin resistance — causative or correlative?

British Journal Of Nutrition ◽

10.1017/s0007114500000982 ◽

2000 ◽

Vol 83 (S1) ◽

pp. S71-S77 ◽

Cited By ~ 261

Author(s):

Keith N. Frayn

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Portal Vein ◽

Visceral Fat ◽

Subcutaneous Fat ◽

Causal Link ◽

Abdominal Fat ◽

High Rate ◽

Fat Accumulation ◽

Visceral Fat Accumulation

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.

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