Abstract

Low birth weight (LBW) associates with increased risk of developing type 2 diabetes. LBW individuals exhibit disproportionately reduced peripheral insulin action and increased fat oxidation after a 5-day high-fat overfeeding (HFO) challenge. Furthermore, LBW men exhibit increased nocturnal fat oxidation during energy balance and low energy expenditure (EE) during fasting. We hypothesized that short-term HFO could further unmask key defects of whole-body energy metabolism in LBW men. Eighteen LBW (2717±268g) and 26 normal birth weight (NBW) (3893±207g) healthy young men were included in a 5-day HFO (60 E% fat, +50% calories) study. The 24-h EE, respiratory quotient and substrate oxidation rates were assessed by indirect calorimetry using respiratory chambers. After adjusting for body composition, the LBW subjects displayed increased nighttime EE (P=0.02) compared with NBW controls during HFO. Nighttime glucose oxidation rate was decreased (P=0.06, adjusted P=0.05), while both adjusted 24-h (P=0.07) and nighttime (P=0.02) fat oxidation rate was elevated in LBW subjects. The relative contribution of fat oxidation to EE was increased in LBW compared with NBW men during the entire 24-h period (P=0.06) and during nighttime (P=0.03). We suggest that disproportionally enhanced fat oxidation in LBW individuals during short-term HFO represents a compensatory response to reduced subcutaneous adipose tissue expandability and storage capacity. The extent to which this mechanism may lead to, or be replaced by insulin resistance, ectopic fat accumulation and/or glucose intolerance during long-term HFO in LBW needs further studies.

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