Energy Expenditure

Energy Expenditure

Energy expenditure is the total energy the body uses over a period of time, usually given in kilocalories per day. It has three main parts. Basal metabolic rate (BMR) is the energy needed to keep vital organs working at rest and makes up about 60-70% of the total. The thermic effect of food (TEF) is the cost of digesting, absorbing and processing food and accounts for roughly 10%. Physical activity energy expenditure (PAEE) varies the most and covers both exercise and everyday movement (non-exercise activity thermogenesis, or NEAT). Total energy expenditure can be measured by indirect calorimetry (which estimates energy use from oxygen taken in and carbon dioxide breathed out) or, in daily life, by the doubly labeled water method.

A basic problem in treating obesity is that weight loss makes the body burn less energy, a response called metabolic adaptation or adaptive thermogenesis. As body mass falls, BMR falls with it, and hormonal changes (such as lower leptin and thyroid hormone levels) can cut energy use further than the loss of active tissue alone would predict. This adaptation is a key cause of weight-loss plateaus and weight regain, so treatments that keep energy use up, or raise it, are especially valuable.

Clinical Relevance to Retatrutide

Retatrutide’s glucagon receptor activity is especially interesting here. Glucagon is a well-known driver of energy use and heat production in the liver, and animal data suggest that activating its receptor can raise whole-body energy use through more fat burning and “futile cycling” in the liver. This may partly offset the drop in energy use that usually comes with weight loss, and so help explain the exceptional weight loss seen with retatrutide in clinical trials. Combining lower intake (through GLP-1 and GIP receptor-driven appetite suppression) with possibly higher energy use (through glucagon receptor activation) sets retatrutide apart from single- and dual-agonist drugs.