Circulating betatrophin/ANGPTL8 levels correlate with body fat distribution in individuals with normal glucose tolerance but not those with glucose disorders.

BACKGROUND: The relationship between betatrophin/ANGPTL8 and obesity has been investigated using body mass index (BMI); however, since BMI reflects overall adiposity rather than body fat distribution, it remains unclear whether fat deposition in different areas of the body affects betatrophin expression. Here, we investigated the correlation between circulating betatrophin levels and body fat distribution in patients with different glucose tolerance. METHODS: We performed a cross-sectional study in 128 participants with impaired glucose tolerance (IGT; n = 64) or normal glucose tolerance (NGT; n = 64). Circulating betatrophin levels were detected by enzyme-linked immunosorbent assay (ELISA). Body fat distribution (subcutaneous, visceral, and limb fat) was measured by magnetic resonance imaging (MRI) and a body fat meter. RESULTS: After controlling for age, sex, and BMI, betatrophin was correlated positively with visceral adipose tissue-to-subcutaneous adipose tissue ratio (VAT/SAT ratio; r = 0.339, p = 0.009) and negatively with body fat ratio (BFR; r = - 0.275, p = 0.035), left lower limb fat ratio (LLR; r = - 0.330, p = 0.011), and right lower limb fat ratio (RLR; r = - 0.288, p = 0.027) in the NGT group, with these correlations remaining after controlling for triglycerides. VAT/SAT ratio (standardized ß = 0.419, p = 0.001) was independently associated with serum betatrophin levels; however, betatrophin was not associated with body fat distribution variables in the IGT group. CONCLUSIONS: Circulating betatrophin levels correlated positively with VAT/SAT ratio and negatively with lower limb fat, but not with subcutaneous or upper limb fat, in individuals with normal glucose tolerance. Thus, betatrophin may be a potential biomarker for body fat distribution in individuals without glucose disorders.

Angiopoietin-like protein 8/betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients.

AIMS/INTRODUCTION: To explore angiopoietin-like protein 8 (ANGPTL-8) levels, and its association with hepatocellular lipid content (HCL) and insulin resistance in patients with different extents of non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: In 48 adults were recruited, of which 12 had no NAFLD (HCL < 5.5%; group 1), 18 had mild NAFLD (5.5% ≤ HCL < 10.0%; group 2) and 18 had moderate-to-severe NAFLD (HCL ≥ 10.0%; group 3). The peripheral insulin sensitivity of all participants was monitored by a hyperinsulinemic-euglycemic clamp (M value), as well as the magnetic resonance image of HCL. Serum ANGPTL-8, blood glucose levels and lipid profiles were also recorded in the study. RESULTS: Group 3 had a worse metabolic profile, and had the highest ANGPTL-8 level (1,129 ± 351 pg/mL vs 742 ± 252 pg/mL, 765 ± 301 pg/mL, P = 0.001) compared with those in group 1 and group 2. In all metabolic profiles, HCL positively correlated the strongest with ANGPTL-8 (r = 0.436, P = 0.042). Multivariate stepwise linear regression analysis showed ANGPTL-8 and alanine aminotransferase were independent determinants of HCL (P = 0.002, P < 0.001, respectively), and these two indexes explained 67.4% of the variation of HCL (P < 0.001). CONCLUSIONS: ANGPTL-8 was positively correlated with hepatocellular lipid content independent of obesity and insulin resistance, indicating that ANGPTL-8 might be a new and important important predictor of the severity of NAFLD.

Ectopic Fat Deposition on Insulin Sensitivity: Correlation of Hepatocellular Lipid Content and M Value.

Purpose. This study aimed to explore the relationship among insulin sensitivity and ectopic fat depots in participants with different glucose status. Methods. Fifty-nine men and women were enrolled in this study: 29 with normal glucose tolerance (NGT), 17 with impaired glucose tolerance (IGT), and 13 with type 2 diabetes mellitus (T2DM). All participants underwent a hyperinsulinemic-euglycemic clamp to assess the insulin sensitivity index (M value) and magnetic resonance imaging to measure the hepatocellular lipid content (HCL), skeletal muscle fat content including intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) of tibialis anterior (ta), and soleus muscle (sol). Results. The M value of NGT group was higher than those of IGT and T2DM groups (P = 0.001). Participants with T2DM had the highest HCL and IMCL (ta) compared with those in NGT and IGT groups (P = 0.001). The M value had an inverse relationship with HCL (r = -0.789, P = 0.001), IMCL (sol) (r = -0.427, P = 0.002), and IMCL (ta) (r = -0.419, P = 0.002). Stepwise linear regression analysis showed that HCL (standardized ß = -0.416; P = 0.001) had an independent relationship with M value. Conclusions. Hepatocellular lipid content deposition happens earlier than skeletal muscle fat deposition. HCL is an independent risk factor for insulin resistance and may be used to evaluate the risk of developing T2DM as a noninvasive marker of insulin sensitivity index.