Effects of Modest Weight Gain On Circulating Free Fatty Acids

Abstract

BackgroundIncreases in circulating free‐fatty acids (FFAs) contribute to obesity‐associated cardiometabolic pathology and may be considered a surrogate marker for adipose tissue dysfunction. However, alterations in FFA metabolism resulting from modest weight gain have not been previously evaluated.ObjectiveExamine the changes in FFAs during modest weight gain in healthy individuals and to investigate the relationship between regional fat depots.Study DesignWe evaluated the effects of overfeeding in 8 healthy, non‐obese participants (4 men; age 29 ± 5.7 years; BMI: 25.1 ± 2.1 kg/m2). FFA concentrations were measured using liquid chromatography/mass spectrometry under fasting conditions and during oral‐glucose tolerance test (OGTT) at baseline and after 8 weeks of weight gain. Prior to the baseline and weight gain visits, subjects consumed isocaloric macro‐nutrient stable diet for three days (50% carbohydrate, 35% fat and 15% protein). Body composition and regional fat depots were assessed using dual‐energy X‐ray absorptiometry and abdominal computed tomography scans.ResultsOverfeeding was accompanied by 3.9 ± 1.6 kg weight gain (p=0.01) resulting from 2.9 ± 0.9 kg (p=0.01) increase in fat mass and 1.0 ± 0.9 kg (p=0.04) increase in fat‐free mass. Compared to baseline, fasting FFA (439 ± 162 μM vs. 368 ± 123 μM, p=0.55) and area under the curve (AUC) for FFA during OGTT (23319 ± 11686 μM. min−1 vs. 20495 ± 4847 μM.min−1, p=0.55) did not change with weight gain. However, at 120 min. of the OGTT FFA were significantly greater after weight gain (60 ± 18 μM vs. 77 ± 34 μM, p=0.04). We found a negative relationship between relative changes in visceral fat area and FFA at 120 min of glucose challenge (rho=−0.76, p=0.03). Furthermore, relative changes in fasting FFA and AUC for FFA during OGTT with weight gain were associated with baseline total fat mass (fasting FFA: rho=0.76, p=0.03; AUC FFA: rho=0.81; p=0.02) and baseline abdominal fat area (fasting FFA: rho=0.76, p=0.03; AUC FFA: rho=0.79; p=0.02).ConclusionsModest weight gain does not alter fasting FFA or overall FFA response to oral glucose challenge. However, our data suggest development of early stages of adipose tissue insulin resistance which is apparent via lesser suppression of FFA at 120 min. of OGTT. Furthermore, the relationships between fasting FFA, AUC‐FFA, and baseline fat mass suggest that individuals with high baseline adiposity may be more susceptible to develop adipose tissue insulin resistance with weight gain.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.