ß-Aminoisobutyric Acid Relates to Favorable Glucose Metabolism through Adiponectin in Adults with Obesity Independent of Prediabetes.

ß-Aminoisobutyric acid (BAIBA) is secreted by skeletal muscle and promotes insulin sensitivity, fat oxidation, and anti-inflammation. While BAIBA is purportedly lower in individuals with obesity, no work has examined if prediabetes (PD) differentially impacts BAIBA concentrations in people with obesity. Methods. Adults were classified as normal glucose tolerant (NGT; n = 22 (20F); 48.0 ± 2.4 yrs; 36.9 ± 1.2 kg/m2) or PD (n = 23 (18F); 54.2 ± 1.6 yrs; 38.4 ± 1.2 kg/m2) based on ADA criteria. A 180-minute 75 g OGTT was used to estimate fasting (HOMA-IR (liver)) and postprandial (Matsuda index (muscle)) insulin sensitivity as well as ß-cell function (disposition index (DI), glucose-stimulated insulin secretion adjusted for insulin sensitivity). Body composition and fasting measures of BAIBA, fat oxidation (indirect calorimetry), and adipokines were determined. Results. NGT and PD had similar BAIBA concentrations (1.4 ± 0.1 vs. 1.2 ± 0.1 µM, P = 0.23) and fat oxidation (P = 0.31), despite NGT having lower fasting (92.2 ± 1.2 vs. 104.1 ± 3.2 mg/dL, P = 0.002) and tAUC180min glucose (P < 0.001) compared to PD. Moreover, NGT had higher postprandial insulin sensitivity (P = 0.01) and higher total phase DIliver (P = 0.003) and DImuscle (P = 0.001). Increased BAIBA was associated with adiponectin (r = 0.37, P = 0.02), adiponectin/leptin ratio (r = 0.39, P = 0.01), and lower glucose and insulin at 180 minutes (r = -0.31, P = 0.03 and r = -0.39, P = 0.03, respectively). Adiponectin also correlated with lower glucose at 180 minutes (r = -0.45, P = 0.005), and mediation analysis showed that BAIBA was no longer a significant predictor of glucose at 180 minutes after controlling for adiponectin (P = 0.08). Conclusion. While BAIBA did not differ between NGT and PD, higher BAIBA is related to favorable glucose metabolism, possibly through an adiponectin-related mechanism. Additional work is required to understand how exercise and/or diet impact BAIBA in relation to type 2 diabetes risk.

A low-calorie diet raises ß-aminoisobutyric acid in relation to glucose regulation and leptin independent of exercise in women with obesity.

Introduction: ß-aminoisobutyric acid (BAIBA) is a suggested cytokine secreted from skeletal muscles that regulates insulin sensitivity, pancreatic function, and fat oxidation. However, no studies to date have examined if a low-calorie diet (LCD) or LCD + with interval exercise (LCD + INT) differentially raises BAIBA. The purpose was to examine if LCD or LCD + INT raises circulating BAIBA in relation to cardiometabolic health. Methods: For this, twenty-three women with obesity were randomized to either 2-weeks of LCD (n = 12, 48.4 ± 2.5 y, 37.84 ± 1.5 kg/m2; ∼1200 kcal/day) or LCD + INT (n = 11, 47.6 ± 4.3 y, 37.9 ± 2.3 kg/m2; ∼60 min/d of INT alternating 3 min of 90% and 50% HRpeak), with matched energy availability. Fasting BAIBA and adipokines along with glucose, insulin, C-peptide, and FFA after every 30 min up to 120 min were obtained during a 75 g OGTT to estimate total area under the curve (tAUC), insulin sensitivity (SIIS), pancreatic function [disposition index (DI)], and hepatic insulin clearance (HIC). Fuel use (indirect calorimetry) was tested at 0, 60, and 120 min of the OGTT along with fitness (VO2peak) and body composition (BodPod). Results: Both treatments lowered body weight (p < 0.001) and leptin (p < 0.001) but raised BAIBA (p = 0.007) and insulin sensitivity (p = 0.02). LCD + INT increased VO2peak (p = 0.02) and REE tAUC120min (p = 0.02) while LCD and LCD + INT decreased carbohydrate oxidation (CHOox) tAUC120min (p < 0.001). Increased BAIBA associated with reduced weight (r = -0.67, p < 0.001), leptin (r = -0.66, p = 0.001), CHOox tAUC120min (r = -0.44, p = 0.03) and DImuscle120min (r = -0.45, p = 0.03), but elevated HIC120min (r = 0.47, p = 0.02). Discussion: Concluding, LCD and LCD + INT increased BAIBA in relation to reduced body weight and pancreatic function in women with obesity. This suggests energy deficit is a key factor regulating circulating BAIBA.