Convergence of adipocyte hypertrophy, telomere shortening and hypoadiponectinemia in obese subjects and in patients with type 2 diabetes

Abstract

Objective: Although telomere shortening has been linked with type 2 diabetes and most variables of adiposity, a shortcoming of such studies is themeasurement of telomere length in leukocytes. Therefore, we tested the association among adipocyte cell size, telomere length (both subcutaneous and visceral adipose tissue) and systemic levels of adiponectin in obese subjects and patients with type 2 diabetes compared to control subjects. Methods: Human subcutaneous and visceral adipose tissues were obtained from the subjects who have undergone bariatric surgery or other abdominal surgeries. The study groups comprised: i) control subjects, ii) type 2 diabetes patients, iii) obese subjects without diabetes and iv) obese subjects with diabetes. Adipocyte cell size wasmeasured by histological staining. Adiponectin levels were measured by ELISA. Telomere length was determined by Real-time PCR and lipid peroxidation was assessed by fluorimetry. Results: Compared to control subjects, adipocyte size (both subcutaneous and visceral) from obese, diabetic and obese–diabetic subjects was significantly larger [pb0.001]. Individuals with adipose hypertrophy also exhibited shortened telomeres and hypoadiponectinemia. Pearson correlation analysis revealed that both visceral and subcutaneous fat cell size showed a positive correlation with FBS, HbA1c, HOMA-IR, LDL, total cholesterol, triglycerides and negatively correlated with HDL and adiponectin. Regression analysis revealed that the association between shortened telomeres and hypoadiponectinemia was lost when adjusted for adipocyte cell size. Conclusion: Adipocyte hypertrophy appears to be strongly associated with shortened telomeres, hypoadiponectinemia and poor glycemic and lipid control. Interestingly, these molecular alterations seen in lean diabetics reflect a state of ‘metabolic obesity’