Significance of adipose tissue characteristics for development of metabolic complications in obesity

Abstract

Background: Obesity is closely related to development of insulin resistance and dyslipidemia. Intrinsic properties of adipose tissue are also of great importance for obesity related comorbidity. The aim of this thesis was to gain further knowledge of adipose depot specific effects of how fat cell size and lipolysis, as well as removal of a large portion of the visceral fat depot, affect metabolic risk.

Methods: All subjects were from a cohort of 81 obese women undergoing gastric bypass operation. Study I and study III were cross-sectional studies using baseline data, whereas study II and IV were longitudinal studies which also included an examination two years post- surgery. Insulin sensitivity was evaluated with hyperinsulinemic euglycemic clamp. Subcutaneous and visceral fat biopsies were obtained to determine mean fat cell size and lipolysis.

Results: Study I showed that subcutaneous fat cell size correlated with insulin sensitivity (r= -0.40 p= 0.004) and visceral fat cell size correlated with dyslipidemia (r=0.32-0.38 p= 0.0006-0.003). Subjects with combined hyperplasia (many small fat cells) in both subcutaneous and visceral fat depots had a favorable metabolic profile compared to subjects with combined hypertrophy (few but large fat cells) (p= 0.0001-0.02).

Study II focused on changes in fat cell size and insulin sensitivity following weight reduction induced by bariatric surgery in obese women. Changes in subcutaneous fat cell size correlated with improved insulin sensitivity independently of changes in subcutaneous fat mass (r=0.32 p= 0.04).

Study III investigated depot specific relations between lipolysis and cardiovascular risk factors. Visceral but not subcutaneous fat cell lipolysis correlated with several cardiovascular risk factors including insulin resistance, high plasma triglycerides and blood pressure (r= 0.28-0.44 p= 0.0001-0.02). Visceral fat cell lipolysis was also increased in subjects with metabolic syndrome (F= 8.3 p= 0.005).

Study IV, designed as a randomized double blind controlled trial, investigated the 2-year effects of omentectomy in conjunction with gastric bypass operation on insulin sensitivity and the lipid profile. Eighty-one subjects were included in the study and 62 were re-examined two years post-surgery. Omentectomy did not give any additional positive metabolic effects, neither in the primary outcome measure insulin sensitivity (p= 0.54), nor the secondary outcome measures such as lipid status or weight reduction (p= 0.17-0.98).

Conclusion: The studies in this thesis highlight that intrinsic factors of adipose tissue, such as fat cell size and lipolysis, independently of fat mass, are important for metabolic complications in obesity. A mere removal of a substantial part of the visceral fat depot does not enhance improved metabolic outcome after gastric bypass operation, suggesting that a metabolic change in adipose tissue and changes in fat cell size are important to achieve positive effects of fat mass reduction.