Accumulating evidence has demonstrated that serum uric acid (UA), a natural powerful antioxidant, plays a beneficial role in bone health in the general population. However, few reports are available on the association between serum UA and bone in patients with type 2 diabetes mellitus (T2DM). We therefore investigated whether the benefit of serum UA for bone health was still present in those patients. 626 males and 609 postmenopausal females with T2DM were enrolled in this cross-sectional study. Serum UA concentrations and bone mineral density (BMD) measured at lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry were obtained from all subjects. Meanwhile, data on osteoporosis prevalence, glucose metabolism, bone turnover markers and other serum biochemical indexes were collected. After adjustment for potential confounders, the results suggested that serum UA was positively associated with BMD in patients with normal weight, but this positive association varied by gender and skeletal sites in overweight T2DM patients [body mass index (BMI) ≥ 25 kg/m]. Moreover, significantly lower odds ratios (ORs) for osteoporosis were found in postmenopausal patients with the highest UA tertile and male patients with medium UA tertile [adjusted OR 0.315, 95% confidence interval (CI) 0.170-0.581 for postmenopausal patients; adjusted OR 0.464, 95% CI 0.225-0.955 for male patients]. The positive association between serum UA and BMD found in Chinese T2DM patients may imply that relatively high UA is a protective factor for bone in these patients. Large intervention studies are needed to further confirm the outcomes and provide possible explanations.

One lead risk signal of obesity-rs1421085 T > C within the FTO gene-is reported to be functional in vitro but lack of organismal evidence. Here, we established global and the brown-adipocyte speci c locusknock-in mice to recapitulate this homologous variant in humans and discovered that mice carrying the C-alleles showed increased thermogenic capacity and a resistance to high-fat diet-induced adiposity with enhanced FTO transcription, while FTO knockdown or inhibition effectively eliminated the increased thermogenic ability of brown adipocytes. In humans, the C-allele was associated with lower birthweight, and its allele frequency increases following the environmental temperature decreases. Cumulatively, these ndings identi ed rs1421085 T > C as a functional variant promoting whole-body thermogenesis and was associated with early human migration from hot to cold environments.

One lead risk signal of obesity–rs1421085 T > C within the FTO gene–is reported to be functional in vitro but lack of organismal evidence. Here, we established global and the brown-adipocyte specific locus-knock-in mice to recapitulate this homologous variant in humans and discovered that mice carrying the C-alleles showed increased thermogenic capacity and a resistance to high-fat diet-induced adiposity with enhanced FTO transcription, while FTO knockdown or inhibition effectively eliminated the increased thermogenic ability of brown adipocytes. In humans, the C-allele was associated with lower birthweight, and its allele frequency increases following the environmental temperature decreases. Cumulatively, these findings identified rs1421085 T > C as a functional variant promoting whole-body thermogenesis and was associated with early human migration from hot to cold environments.