Lu, Yingli

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

Abstract Context Previous epidemiological studies had inconsistent results regarding the relationship between blood lead level (BLL) and adiposity. Objective We aimed to investigate the associations of BLL with body mass index (BMI) particularly using Mendelian randomization analyses and examine the interaction between obesity-predisposing genes and BLL on the associations. Design and Setting A total of 3922 participants were enrolled from 16 sites in East China in 2014 from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic risk score (GRS) based on 29 variants that were identified and validated in East Asians. BLL was measured by atomic absorption spectrometry. Main Outcome Measure BMI was calculated, and BMI ≥25 kg/m2 was defined as overweight. Results Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (β = 0.24; 95% CI, 0.08 to 0.40; P < 0.001) and each 1-point increase in BMI-GRS (β = 0.08; 95% CI, 0.05 to 0.11; P < 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were −0.003 (95% CI, −0.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI ≥25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to 2.05) in the highest quartile of GRS, but no significant associations were found in the lower three quartiles. Conclusions The associations of BLL with BMI and overweight (BMI ≥25 kg/m2) were significantly modulated by BMI genetic susceptibility.

Background. The strength of associations between total testosterone (TT) and metabolic parameters may vary in different nature of population structure; however, no study has ever given this information in Chinese population, especially those without metabolic syndrome (MS). We aimed to analyze the association magnitudes between TT and multiple metabolic parameters in general Chinese men. Methods. 4309 men were recruited from SPECT-China study in 2014-2015, which was performed in 22 sites in East China. TT, weight status, and various metabolic parameters were measured. Linear and logistic regressions were used to analyze the associations. Results. Men in lower TT quartiles had worse metabolic parameters including body mass index, triglycerides, HbA1c, and HOMA-IR (all P for trend < 0.001). Body mass index (B −0.32, 95%CI −0.35 to −0.29) and obesity (OR 0.40, 95%CI 0.35–0.45) had the largest association magnitude per one SD increment in TT, while blood pressure and hypertension (OR 0.90, 95%CI 0.84–0.98) had the smallest. These associations also persisted in individuals without metabolic syndrome. Conclusions. Obesity indices had closer relationships with TT than most other metabolic measures with blood pressure the least close. These associations remained robust after adjustment for adiposity and in subjects without metabolic syndrome.