Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management-A State-of-the-Art Narrative Review

Abstract

The global rise in obesity underscores the need for effective weight management strategies that address individual metabolic and hormonal variability, moving beyond the simplistic "calories in, calories out" model. Body types-ectomorph, mesomorph, and endomorph-provide a framework for understanding the differences in fat storage, muscle development, and energy expenditure, as each type responds uniquely to caloric intake and exercise. Variability in weight outcomes is influenced by factors such as genetic polymorphisms and epigenetic changes in hormonal signaling pathways and metabolic processes, as well as lifestyle factors, including nutrition, exercise, sleep, and stress. These factors impact the magnitude of lipogenesis and myofibrillar protein synthesis during overfeeding, as well as the extent of lipolysis and muscle proteolysis during caloric restriction, through complex mechanisms that involve changes in the resting metabolic rate, metabolic pathways, and hormonal profiles. Precision approaches, such as nutrigenomics, indirect calorimetry, and artificial-intelligence-based strategies, can potentially leverage these insights to create individualized weight management strategies aligned with each person's unique metabolic profile. By addressing these personalized factors, precision nutrition offers a promising pathway to sustainable and effective weight management outcomes. The main objective of this review is to examine the metabolic and hormonal adaptations driving variability in weight management outcomes and explore how precision nutrition can address these challenges through individualized strategies.

Keywords: artificial intelligence; calories in; calories out model; carbohydrate–insulin model; dominant energy balance model; metabolism; muscle mass; obesity; precision nutrition; weight loss; weight management.

Figure 1

Key adaptations to caloric restriction affecting weight loss and body composition. Abbreviations. BMR (Basal Metabolic Rate); FFAs (Free Fatty Acids); GLP-1 (Glucagon-Like Peptide-1); GH (Growth Hormone); HSL (Hormone-Sensitive Lipase); PYY (Peptide YY); rT3 (Reverse Triiodothyronine); SNS (Sympathetic Nervous System); T3 (Triiodothyronine); UCP1 (Uncoupling Protein 1).

Figure 2

Key adaptations to overfeeding affecting weight gain and body composition. Abbreviations. BMR (Basal Metabolic Rate); C/EBPα (CCAAT/Enhancer-Binding Protein Alpha); GLP-1 (Glucagon-Like Peptide-1); IGF-I (Insulin-Like Growth Factor I); LPL (Lipoprotein Lipase); PPARγ (Peroxisome Proliferator-Activated Receptor Gamma); PYY (Peptide YY); SNS (Sympathetic Nervous System); T3 (Triiodothyronine); T4 (Thyroxine); UCP1 (Uncoupling Protein 1).