Low expression of brown and beige fat genes in subcutaneous tissues in obese patients

Arch Med Sci. 2019 Sep;15(5):1113-1122. doi: 10.5114/aoms.2018.76684. Epub 2018 Jun 25.

Abstract

Introduction: The molecular mechanisms behind obesity pathogenesis remain largely undefined. Impairment in the browning process of subcutaneous tissues proposed to contribute to obesity pathogenesis. In the current study, we aimed to assess whether the expression of brown fat genes in subcutaneous tissues in obese patients is altered as compared to non-obese patients.

Material and methods: Participants were recruited from patients undergoing general surgeries. At the same site of surgery, biopsies were taken from the abdominal subcutaneous tissues from each participant, along with a venous blood sample. The expression of BAT genes was measured using a real-time PCR method. Serum FGF21 was measured using an ELISA kit, and the serum blood lipid profile was measured using the Dimension VistaTM 1500 System.

Results: A total of 58 surgical patients was involved. A low expression of BAT genes was observed in the groups with higher body mass index (BMI) (< 30 kg/m2) as compared to the groups with lower BMI (> 30 kg/m2). The expression of CIDEA and CITED1 was significantly higher in the patients with normal weight as compared to obese (p = 0.01 and p = 0.02, respectively). A significant negative correlation was found between the expression of BAT genes and BMI in patients with BMI < 35 kg/m2. However, the strongest negative correlation was observed in the expression of CIDEA (r = -0.5, p = 0.004), followed by TBX1 (r = -0.4, p = 0.01), CITED1, and ZIC1 (r = -0.4, p = 0.03). Whereas the correlation of UCP1 with BMI remained insignificant (r = -0.29, p = 0.08). When including patients with BMI > 35 kg/m2, the correlation decreased and became insignificant (p = 0.08). No significant correlation was found between the expression of BAT genes and blood lipid profiles (p > 0.05). Serum FGF21 was positively and significantly correlated to the expression of UCP1 (r = 0.56, p = 0.02) and TBX1 (r = 0.62, p = 0.01), however, this correlation was missing in patients with severe obesity.

Conclusions: Our data suggested that brown and beige genes expression in abdominal subcutaneous tissues is dysregulated in patients with obesity. Further studies are needed to investigate the role of browning of subcutaneous tissues in regulating body weight and metabolism in human.

Keywords: CIDEA; CITED1; TBX1; ZIC1; uncoupling protein 1.