Changes in fat mass influence SREBP-1c and UCP-2 gene expression in formerly obese subjects.

Objective: To investigate the effect of fat mass (FM) reduction on adipose tissue gene expression in terms of lipid synthesis [sterol regulatory binding protein 1c (SREBP-1c)] and lipid oxidation [uncoupling protein 2 (UCP-2)] 2 years after lipid malabsorption and to assess the influence of lipid malabsorption on fat-free mass (FFM) maintenance evaluating the expression of genes related to glycolysis [hexokinase (HKII)] and glucose storage [glycogen synthase (GS)].

Research Method And Procedures: SREBP-1c, UCP-2, HKII, and GS mRNA expression were studied by reverse transcriptase-competitive polymerase chain reaction in 10 massively obese subjects before and 2 years after bilio-pancreatic diversion (BPD). Body composition was assessed by isotopic dilution method and insulin sensitivity by euglycemic-hyperinsulinemic clamp.

Results: FM decrease was approximately 60%, whereas FFM remained at normal physiological levels. In adipose tissue, SREBP-1c mRNA reduction (-39%, p < 0.005) was related only to FM changes after BPD, and UCP-2 decrease (-37%, p < 0.05) was dependent on free fatty acid (FFA) changes. No significant variations were observed in HKII and GS gene expression in skeletal muscle.

Discussion: Lipid malabsorption induced by BPD altered the expression of genes involved in glucose and lipid metabolism, with different consequences on FM and FFM. The degree of FM loss seems to interfere with SREBP-1c gene suppression to preserve an adequate amount of fat storage, in accordance with the thrifty genotype hypothesis. The reduction of FFAs induced by BPD acts in inhibiting FFA transportation to the mitochondria (UCP-2), contributing to the decreased lipid oxidation inside the adipose tissue.