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

Abstract

It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a "metabolic sink." However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a "metabolic sink."

Keywords: adipose tissue distribution; lipectomy; metabolic sink; muscle; subcutaneous adipose issue; triglyceride; visceral adipose tissue.

Figure 1.

4-week glucose tolerance test (GTT) and subsequent insulin concentrations of Chow and HFD Sham and IngX mice. (A) IngX in Chow mice did not alter glucose tolerance, or (C) insulin concentration. (A) IngX in HFD mice significantly increased glucose concentration at 60 and 120 minutes (P ≤ 0.05; *= compared with HFD Sham) and (B) area under the curve of the GTT (P ≤ 0.05; * = compared with all other groups). (C) Subsequent insulin concentration was increased in HFD IngX groups, with significant increase at 120 minutes (P ≤ 0.05; *= compared with sham controls).

Figure 2.

Tissue triglyceride concentration 5 weeks after Sham or IngX surgery in Chow and HFD mice. (A) Muscle triglyceride concentration was significantly increased in Chow and HFD adipose tissue removal groups. (B) Liver triglyceride concentration was significantly decreased in HFD mice with IngX (Unlike letters indicate significance; P ≤ 0.05).

Figure 3.

Muscle insulin sensitivity, pAKT/AKT 5 weeks after surgery. (A) Saline injected mice. (B) IngX reduced insulin-stimulated pAKT/AKT in both Chow and HFD groups, the greatest decrease occurred in HFD ingX mice (Unlike letters indicate significance; P ≤ 0.05).

Figure 4.

Visceral and subcutaneous adipose tissue gene expression 5 weeks post-surgery. Vegf (A) and Pparγ (B) expression was significantly increased in the visceral depot of IngX Chow animals, whereas Lpl (C) was decreased. In the residual non-excised portion of the subcutaneous depot Vegf expression (D) was significantly increased in the IngX HFD-fed group, whereas Pparγ (E) and Lpl (F) expression were significantly increased in IngX Chow mice only (Unlike letters indicate significance; P ≤ 0.05).

Figure 5.

Liver gene expression 5 weeks post-surgery. IngX increased the expression of factors that play a role in fibrosis and collagen production in HFD mice only (B and C; Unlike letters indicate significance; P ≤ 0.05).

Figure 6.

Glucose tolerance test (GTT) and subsequent insulin concentrations (A-C) Following long-term HFD feeding or (D-F) in mice with preceding glucose intolerance. (C) 12 weeks post-surgery insulin concentration was significantly increased at 15 minutes in HFD IngX mice (P ≤ 0.05; compared with HFD Sham). IngX did not alter GTT (D) or insulin measurements (F) in mice with preceding glucose intolerance. With AUC unlike letters indicate significance; P ≤ 0.05.

Figure 7.

Femoral muscle triglyceride (A and B) was significantly increased in HFD groups compared with Chow. In 13 week experiment IngX-induced increases in femoral muscle triglyceride concentration only occurred in Chow mice (Unlike letters indicate significance; P ≤ 0.05).

Figure 8.

(A) Subcutaneous adipose tissue depot location, dorsal and ventral. (B) Inguinal adipose tissue depot before removal, and (C) after ∼300mg removal.