Physiological protection against weight gain: evidence from overfeeding studies and future directions
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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Physiological protection against weight gain : evidence from overfeeding studies and future directions. / Lund, Jens; Clemmensen, Christoffer.
I: Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Bind 378, Nr. 1885, 2022.0229, 2023.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - Physiological protection against weight gain
T2 - evidence from overfeeding studies and future directions
AU - Lund, Jens
AU - Clemmensen, Christoffer
PY - 2023
Y1 - 2023
N2 - Body weight is under physiological regulation. When body fat mass decreases, a series of responses are triggered to promote weight regain by increasing food intake and decreasing energy expenditure. Analogous, in response to experimental overfeeding, excessive weight gain is counteracted by a reduction in food intake and possibly by an increase in energy expenditure. While low blood leptin and other hormones defend against weight loss, the signals that oppose overfeeding-induced fat mass expansion are still unknown. In this article, we discuss insights gained from overfeeding interventions in humans and intragastric overfeeding studies in rodents. We summarize the knowledge on the relative contributions of energy intake, energy expenditure and energy excretion to the physiological defence against overfeeding-induced weight gain. Furthermore, we explore literature supporting the existence of unidentified endocrine and non-endocrine pathways that defend against weight gain. Finally, we discuss the physiological drivers of constitutional thinness and suggest that overfeeding of individuals with constitutional thinness represents a gateway to understand the physiology of weight gain resistance in humans. Experimental overfeeding, combined with modern multi-omics techniques, has the potential to unveil the long-sought signalling pathways that protect against weight gain. Discovering these mechanisms could give rise to new treatments for obesity. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.
AB - Body weight is under physiological regulation. When body fat mass decreases, a series of responses are triggered to promote weight regain by increasing food intake and decreasing energy expenditure. Analogous, in response to experimental overfeeding, excessive weight gain is counteracted by a reduction in food intake and possibly by an increase in energy expenditure. While low blood leptin and other hormones defend against weight loss, the signals that oppose overfeeding-induced fat mass expansion are still unknown. In this article, we discuss insights gained from overfeeding interventions in humans and intragastric overfeeding studies in rodents. We summarize the knowledge on the relative contributions of energy intake, energy expenditure and energy excretion to the physiological defence against overfeeding-induced weight gain. Furthermore, we explore literature supporting the existence of unidentified endocrine and non-endocrine pathways that defend against weight gain. Finally, we discuss the physiological drivers of constitutional thinness and suggest that overfeeding of individuals with constitutional thinness represents a gateway to understand the physiology of weight gain resistance in humans. Experimental overfeeding, combined with modern multi-omics techniques, has the potential to unveil the long-sought signalling pathways that protect against weight gain. Discovering these mechanisms could give rise to new treatments for obesity. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.
KW - body weight
KW - constitutional thinness
KW - endocrinology
KW - energy homeostasis
KW - obesity
KW - overfeeding
U2 - 10.1098/rstb.2022.0229
DO - 10.1098/rstb.2022.0229
M3 - Review
C2 - 37482786
AN - SCOPUS:85165602145
VL - 378
JO - Philosophical Transactions of the Royal Society B: Biological Sciences
JF - Philosophical Transactions of the Royal Society B: Biological Sciences
SN - 0962-8436
IS - 1885
M1 - 2022.0229
ER -
ID: 360860528