The effect of fat removal on glucose tolerance is depot specific in male and female mice

Abstract

Shi H, Strader AD, Woods SC, Seeley RJ. The effect of fat removal on glucose tolerance is depot specific in male and female mice. Am J Physiol Endocrinol Metab 293: E1012-E1020, 2007. First published July 24, 2007; doi:10.1152/ajpendo.00649.2006-Energy is stored predominately as lipid in white adipose tissue (WAT) in distinct anatomical locations, with each site exerting different effects on key biological processes, including glucose homeostasis. To determine the relative contributions of subcutaneous and visceral WAT on glucose homeostasis, comparable amounts of adipose tissue from abdominal subcutaneous inguinal WAT (IWAT), intra-abdominal retroperitoneal WAT (RWAT), male gonadal epididymal WAT (EWAT), or female gonadal parametrial WAT (PWAT) were removed. Gonadal fat removal in both male and female chow-fed lean mice resulted in lowered glucose levels across glucose tolerance tests. Female lean C57BL/6J mice as well as male and female lean FVBN mice significantly improved glucose tolerance, indicated by decreased areas under glucose clearance curves. For the C57BL/6J mice maintained on a high-fat butter-based diet, glucose homeostasis was improved only in female mice with PWAT removal. Removal of IWAT or RWAT did not affect glucose tolerance in either dietary condition. We conclude that WAT contribution to glucose homeostasis is depot specific, with male gonadal EWAT contributing to glucose homeostasis in the lean state, whereas female gonadal PWAT contributes to glucose homeostasis in both lean and obese mice. These data illustrate both critical differences among various WAT depots and how they influence glucose homeostasis and highlight important differences between males and females in glucose regulation. intra-abdominal fat; subcutaneous fat; adipokine; portal drainage ENERGY IS PREDOMINATELY STORED AS LIPID in white adipose tissue (WAT), and WAT from different anatomical locations has been implicated in the regulation of a wide array of metabolic parameters. Abdominal obesity with excessive subcutaneous abdominal and intra-abdominal WAT, for example, is associated with increased insulin resistance. One hypothesis is that intra-abdominal WAT has a disproportionately adverse effect on glucose homeostasis (7,10,27,42,44), and this concept is supported by several human studies (12, 15, 37) but challenged in others (1, 2, 18, 30) that suggest that subcutaneous abdominal WAT is more closely related with insulin resistance.The surgical removal of WAT, i.e., by liposuction or lipectomy, has been used to study the relationship between abdominal obesity and insulin resistance in humans and rodents. Liposuction of obese women that causes a sizable reduction of subcutaneous abdominal fat results in no improvement in insulin sensitivity, plasma glucose, or insulin levels (25). Improvement of insulin resistance after removal of certain WAT depots in rat obese models provides direct evidence for the causal role of these fat pads in causing insulin resistance. For example, simultaneous removal of both gonadal epididyma...

Lower body adipose tissue removal decreases glucose tolerance and insulin sensitivity in mice with exposure to high fat diet

“…Consistent with this other have demonstrated LBSAT removal in obese/glucose intolerant mice is without metabolic effect. 25 The present study supports the notion that IngXmediated perturbations to glucose homeostasis are sustained at longer durations, but are influenced by the pre-existing metabolic milieu. HFD consequences of IngX are greatest early post-surgery, attenuated following a longer post-surgical duration and don't occur if obesity/glucose intolerance is present at surgery.…”

“…Whereas in chow or high fat diet-fed mice the removal of LBSAT (inguinal depot) had no effect on glucose regulation, 25 its removal in Syrian hamsters resulted in hypertriglyceridemia and increased liver lipid deposition. 26 Differences between these 2 rodent studies may be linked to the species used, the amount of tissue removed (15 vs 50%), location of the depots that were removed and/or the duration of the study (»3 vs. Twelve wks).…”

Implicações da lipoclasia dermossônica no metabolismo energético e na composição corporal de ratos Wistar saudáveis

“…They also report that the increased FFA flow originating from adipose tissues to non-adipose ones, in general worsens the signaling of the insulin receptor substrate 1 (IRS-1) [21][22][23][24][25][26][27] , suggesting that the IR observed in the animals treated with DLC might have occurred due to the lipotoxic effects of the FFA in the IRS-1 signaling, bringing about dysfunctions in the activation cascade of this receptor [18][19][20][21] , which was indicated by the high values of HOMA-IR. Other studies show that the inhibition and/or loss of sensibility of the IRS-1 may facilitate the accumulation of tissue fat through the reduction of the lipolytic activity of the insulin, leading to the resterification of the FFA in the muscles and other tissues, a critical effect which is currently being discussed as lipotoxicity [17][18][19][20][21][22][23][24] .…”

“…Therefore, the goal of this study was to evaluate the implications of DLC on the energetic metabolism and body fat distribution of healthy rats, by means of measurements such as weight, length, plasma biochemistry, body composition (obesity index) 26 and bilateral lipectomy of the fat depositions 27 .…”

Sex Differences in Obesity-Related Glucose Intolerance and Insulin Resistance

“…When various strains of mice are subjected to glucose tolerance tests, female mice have lower glucose levels than male mice at different time point throughout the tests (141)(142)(143). Additionally, female mice show a greater fall in blood glucose in response to insulin as compared with male mice during insulin tolerance tests (141)(142)(143).…”