Abstract
Human biology has evolved to keep body fat within a range that supports survival. During the last 25 years, obesity biologists have uncovered key aspects of physiology that prevent fat mass from becoming too low. In contrast, the mechanisms that counteract excessive adipose expansion are largely unknown. Evidence dating back to the 1950s suggests the existence of a blood-borne molecule that defends against weight gain. In this article, we discuss the research supporting an "unidentified factor of overfeeding" and models that explain its role in body weight control. If it exists, revealing the identity of this factor could end a long-lasting enigma of energy balance regulation and facilitate a much-needed breakthrough in the pharmacological treatment of obesity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipose Tissue / metabolism
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Animals
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Appetite Depressants / blood
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Appetite Depressants / metabolism*
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Body Weight / physiology*
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Hormones / blood
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Hormones / metabolism*
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Humans
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Hyperphagia / genetics
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Hyperphagia / metabolism
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Obesity / genetics
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Obesity / metabolism
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Parabiosis
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Weight Gain / physiology
Substances
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Appetite Depressants
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Hormones
Grants and funding
JL is supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant number NNF17SA0031406. CC receives funding from the Lundbeck Foundation (Fellowship R238-2016-2859) and the Novo Nordisk Foundation (grant number NNF17OC0026114). Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center, based at the University of Copenhagen, Denmark, and partially funded by an unconditional donation from the Novo Nordisk Foundation (
www.cbmr.ku.dk) (Grant number NNF18CC0034900). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.