RESUMEN
BACKGROUND: Low-calorie diet (LCD)-induced weight loss demonstrates response heterogeneity. Physiologically, a decrease in energy expenditure lower than what is predicted based on body composition (metabolic adaptation) and/or an impaired capacity to increase fat oxidation may hinder weight loss. Understanding the metabolic components that characterize weight loss success is important for optimizing weight loss strategies. OBJECTIVES: We tested the hypothesis that overweight/obese individuals who had lower than expected weight loss in response to a 28-d LCD would be characterized by 1) impaired fat oxidation and 2) whole-body metabolic adaptation. We also characterized the molecular mechanisms associated with weight loss success/failure. METHODS: This was a retrospective comparison of participants who met their predicted weight loss targets [overweight/obese diet sensitive (ODS), n = 23, females = 21, males = 2] and those that did not [overweight/obese diet resistant (ODR), n = 14, females = 12, males = 2] after a 28-d LCD (900-1000 kcal/d). We used whole-body (energy expenditure and fat oxidation) and tissue-specific measurements (metabolic proteins in skeletal muscle, gene expression in adipose tissue, and metabolites in serum) to detect metabolic properties and biomarkers associated with weight loss success. RESULTS: The ODR group had greater mean ± SD metabolic adaptation (-175 ± 149 kcal/d; +119%) than the ODS group (-80 ± 108 kcal/d) after the LCD (P = 0.030). Mean ± SD fat oxidation increased similarly for both groups from baseline (0.0701 ± 0.0206 g/min) to day 28 (0.0869 ± 0.0269 g/min; P < 0.001). A principal component analysis factor comprised of serum 3-hydroxybutyric acid, citrate, leucine/isoleucine, acetyl-carnitine, and 3-hydroxylbutyrlcarnitine was associated with weight loss success at day 28 (std. ß = 0.674, R2 = 0.479, P < 0.001). CONCLUSIONS: Individuals who achieved predicted weight loss targets after a 28-d LCD were characterized by reduced metabolic adaptation. Accumulation of metabolites associated with acetyl-CoA excess and enhanced ketogenesis was identified in the ODS group.This trial was registered at clinicaltrials.gov as NCT01616082.
Asunto(s)
Adaptación Fisiológica/fisiología , Dieta Reductora , Ingestión de Energía , Metabolismo Energético/fisiología , Sobrepeso , Pérdida de Peso , Adulto , Biomarcadores , Composición Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estudios Retrospectivos , Factores de TiempoRESUMEN
OBJECTIVE: Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-ß (Aß) precursor protein and associated ß- and γ-secretases are expressed in adipose tissue. Aß precursor protein is up-regulated with obesity and correlated to insulin resistance. Aß may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and Aß may exert effects on adipose tissue insulin receptor signaling. METHODS: Human stromal-vascular cells and differentiated adipocytes were cultured with different combinations of glucose and insulin and then assayed for Aß in conditioned media. Aß was measured in vivo using adipose tissue microdialysis. RESULTS: Aß secretion was increased by glucose and insulin in vitro. Adipose tissue microdialysates contained Aß. Adipocytes treated with Aß had decreased expression of insulin receptor substrate-2 and reduced Akt-1 phosphorylation. CONCLUSIONS: Aß was made by adipose tissue cells in vitro at concentrations similar to in vivo measurements. Regulation of Aß production by glucose and insulin and effects of Aß on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.