Fibroblast Growth Factor 21 Facilitates the Homeostatic Control of Feeding Behavior

Abstract

Fibroblast growth factor 21 (FGF21) is a stress hormone that is released from the liver in response to nutritional and metabolic challenges. In addition to its well-described effects on systemic metabolism, a growing body of literature now supports the notion that FGF21 also acts via the central nervous system to control feeding behavior. Here we review the current understanding of FGF21 as a hormone regulating feeding behavior in rodents, non-human primates, and humans. First, we examine the nutritional contexts that induce FGF21 secretion. Initial reports describing FGF21 as a ‘starvation hormone’ have now been further refined. FGF21 is now better understood as an endocrine mediator of the intracellular stress response to various nutritional manipulations, including excess sugars and alcohol, caloric deficits, a ketogenic diet, and amino acid restriction. We discuss FGF21’s effects on energy intake and macronutrient choice, together with our current understanding of the underlying neural mechanisms. We argue that the behavioral effects of FGF21 function primarily to maintain systemic macronutrient homeostasis, and in particular to maintain an adequate supply of protein and amino acids for use by the cells.

Relationship between dietary macronutrient composition with weight loss after bariatric surgery: A systematic review

“…FGF21 increases appetite and total caloric intake to stimulate protein intake. 40,41 Furthermore, induction of thermogenesis is one of the main mechanisms responsible for the satiety effect of proteins. The body uses 20% to 30% of the caloric value of protein to metabolize and store it, compared with 5% to 10% for carbohydrates and only 0% to 3% for lipids.…”

“…eIF2α increases the specific translation of specific factors like transcription factor 4 (ATF4) that targets FGF21. FGF21 increases appetite and total caloric intake to stimulate protein intake 40,41 …”

Protein appetite as an integrator in the obesity system: the protein leverage hypothesis

“…Under pharmacological administration of FGF21, mice and rats increase total food intake on a fixed diet, and exhibit a shift in macronutrient selection when offered a choice of foods, selectively increasing protein intake and demonstrating reduced sweet preference (at least when animals are simultaneously carbohydrate replete) [56][57][58][59][60][61][62][63]). When mice can select between foods of different macronutrient compositions, FGF21 administration has little or no effect on total energy intake, indicating that increased intake on no-choice, low-protein diets is driven by compensatory feeding for protein, rather than being a secondary response to FGF21induced elevated energy expenditure [57,58,62,64]. Rather, it would appear that elevation of energy expenditure is a mechanism for voiding excess ingested calories driven by protein leverage, thereby maintaining body composition despite hyperphagia.…”

The development of blood protein profiles in extremely preterm infants follows a stereotypic evolution pattern

“…2a, where the levels of broblast growth factor 21 (FGF-21) is shown from birth to full-term age (PMW 40). FGF-21 is a protein involved in metabolism and growth by regulating insulin sensitivity and glucose uptake 21 . We observed higher levels with increasing postnatal age of the infant (Fig.…”