Endocrine Abstracts

Background: Adipose tissue dysfunction, such as adipocyte hypertrophy and secretion of pro-inflammatory cytokines, develops in obese subjects and goes hand in hand with obesity-related complications, especially insulin resistance (IR) and systemic inflammation. The exact mechanisms underlying adipose tissue dysfunction and consequently the obesity-related complications are not yet fully understood.

Aim: Investigate the association between systemic IR and inflammation, and markers of adipose tissue dysfunction during weight loss in a severely obese population.

Subjects and methods: Eighteen obese subjects (age 50±11 years, BMI 43.7±5.6 kg/m², 12 men) were recruited prior to adhering dedicated lifestyle changes (n=4) or undergoing gastric bypass surgery (n=14). Before start of weight loss, and six months and one year thereafter, subcutaneous abdominal adipose tissue (SAT) and fasting serum was collected. C-reactive protein (CRP), glucose and insulin were determined using standard laboratory assays. Homeostasis model assessment-estimated IR (HOMA-IR) was calculated. mRNA expression in SAT of glucose transporter 4 (GLUT4), bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), interleukin-10 (IL10), interleukin-33 (IL33) and tumor necrosis factor alpha (TNFα) were determined using qPCR.

Results: Before weight loss, median fasting glucose level was 5.5 (4.8–5.8) mmol/l and insulin level was 159.7 (76.4–208.4) pmol/l. At baseline, no correlations were found between BMI, CRP levels or HOMA-IR, and SAT expression of GLUT4, BMP4, IL6, IL10, IL33 and TNFα. During follow-up, BMI decreased to 32.6 kg/m² after six months and 29.7 kg/m² after one year (P<0.001), as did CRP levels and HOMA-IR (all, P<0.005). SAT expression of IL6 and TNFα significantly decreased (F(2,13.853)=10.191, P=0.002 and F(2,16.636)=4.009, P=0.038; respectively), while no changes in IL10 and IL33 mRNA levels were observed. mRNA levels of GLUT4 significantly increased after start of weight loss (F(2,25.177)=3.459, P=0.047), while for BMP4 no change was observed (F(2,13.289)=2.056, P=0.167). A positive trend between the change of CRP levels and change of HOMA-IR between baseline and six months was found (r_s=0.470, P=0.077) and also positive correlations between change in mRNA TNFα levels and change in HOMA-IR, CRP and BMI during follow-up (all, P<0.05).

Discussion: Weight loss in a severely obese population leads to decreases in systemic inflammation and IR. In addition, expression of certain pro-inflammatory cytokines in SAT was lower, and expression of GLUT4 was higher six months after start of weight loss. Moreover, changes in SAT TNFα expression during weight loss are correlated with improvements in systemic inflammatory status and IR.