Rhythmic Diurnal Gene Expression in Human Adipose Tissue From Individuals Who Are Lean, Overweight, and Type 2 Diabetic

OBJECTIVE: Previous animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach of analyzing serial human WAT biopsies across a 24-h cycle in controlled laboratory conditions. RESEARCH DESIGN AND METHODS: Lean (n = 8), overweight/obese (n = 11), or overweight/obese type 2 diabetic (n = 8) volunteers followed a strict sleep–wake and dietary regimen for 1 week prior to the laboratory study. They were then maintained in controlled light–dark conditions in a semirecumbent posture and fed hourly during wake periods. Subcutaneous WAT biopsies were collected every 6 h over 24 h, and gene expression was measured by quantitative PCR. RESULTS: Lean individuals exhibited significant (P < 0.05) temporal changes of core clock (PER1, PER2, PER3, CRY2, BMAL1, and DBP) and metabolic (REVERBα, RIP140, and PGC1α) genes. The BMAL1 rhythm was in approximate antiphase with the other clock genes. It is noteworthy that there was no significant effect (P > 0.05) of increased body weight or type 2 diabetes on rhythmic gene expression. CONCLUSIONS: The robust nature of these rhythms and their relative phasing indicate that WAT now can be considered as a peripheral tissue suitable for the study of in vivo human rhythms. Comparison of data between subject groups clearly indicates that obesity and type 2 diabetes are not related to the amplitude of rhythmic WAT gene expression in humans maintained under controlled conditions.