Energy Metabolism, Fuel Selection and Body Weight Regulation
Overview
Authors
Affiliations
Energy homeostasis is critical for the survival of species. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an 'obesogenic' environment. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. The concept of metabolic flexibility and its impact on body weight regulation is also presented.
Advances in Oral Biomacromolecule Therapies for Metabolic Diseases.
Jiao Q, Huang Y, He J, Xu Y Pharmaceutics. 2025; 17(2).
PMID: 40006605 PMC: 11859201. DOI: 10.3390/pharmaceutics17020238.
Yue L, Yan Y Int J Chron Obstruct Pulmon Dis. 2025; 20:373-388.
PMID: 39991071 PMC: 11846517. DOI: 10.2147/COPD.S491687.
Lyu C, Kang S, Shao H, Kim D, Jung H Mol Med Rep. 2025; 31(3).
PMID: 39886968 PMC: 11795245. DOI: 10.3892/mmr.2025.13440.
MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis.
Chourasia S, Petucci C, Shoffler C, Abbasian D, Wang H, Han X EMBO J. 2025; 44(4):1007-1038.
PMID: 39753955 PMC: 11832942. DOI: 10.1038/s44318-024-00335-7.
Spinal afferent neurons: emerging regulators of energy balance and metabolism.
Jarrah M, Tasabehji D, Fraer A, Mokadem M Front Mol Neurosci. 2024; 17:1479876.
PMID: 39582948 PMC: 11583444. DOI: 10.3389/fnmol.2024.1479876.