Central and Peripheral Regulation of Food Intake and Physical Activity: Pathways and Genes
Open accessAbstract
A changing environment and lifestyle on the background of evolutionary engraved and perinatally imprinted physiological response patterns is the foremost explanation for the current obesity epidemic. However, it is not clear what the mechanisms are by which the modern environment overrides the physiological controls of appetite and homeostatic body‐weight regulation. Food intake and energy expenditure are controlled by complex, redundant, and distributed neural systems involving thousands of genes and reflecting the fundamental biological importance of adequate nutrient supply and energy balance. There has been much progress in identifying the important role of hypothalamus and caudal brainstem in the various hormonal and neural mechanisms by which the brain informs itself about availability of ingested and stored nutrients and, in turn, generates behavioral, autonomic, and endocrine output. Some of the genes involved in this “homeostatic” regulator are crucial for energy balance as manifested in the well‐known monogenic obesity models. However, it can be clearly demonstrated that much larger portions of the nervous system of animals and humans, including the cortex, basal ganglia, and the limbic system, are concerned with the procurement of food as a basic and evolutionarily conserved survival mechanism to defend the lower limits of adiposity. By forming representations and reward expectancies through processes of learning and memory, these systems evolved to engage powerful emotions for guaranteed supply with, and ingestion of, beneficial foods from a sparse and often hostile environment. They are now simply overwhelmed with an abundance of food and food cues no longer contested by predators and interrupted by famines. The anatomy, chemistry, and functions of these elaborate neural systems and their interactions with the “homeostatic” regulator in the hypothalamus are poorly understood, and many of the genes involved are either unknown or not well characterized. This is regrettable because these systems are directly and primarily involved in the interactions of the modern environment and lifestyle with the human body. They are no less “physiological” than metabolic‐regulatory mechanisms that have attracted most of the research during the past 15 years.
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Regulation of body weight is asymmetrical: whilst the reduction in body weight is strongly defended, physiology does not resist an increase in fat mass.
“An alternative view that has been discussed for decades is that regulation is asymmetrical [34]. Whilst the reduction in body weight is strongly defended, physiology does not resist an increase in fat mass [35].”
From Appetite control and energy balance: Impact of exercise (2015) · cites this paper as [35]
Food intake and energy expenditure are controlled by complex, redundant, and distributed neural systems, likely involving thousands of genes and reflecting the fundamental biological importance of adequate nutrient supply and energy balance.
“Food intake and energy expenditure are thought to be controlled by complex, redundant, and distributed neural systems, likely involving thousands of genes and reflecting the fundamental biological importance of adequate nutrient supply and energy balance”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [103]
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- Authors
- Lenard, N. R., & Berthoud, H.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Berthoud, Hans‐Rudolf
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2008-12
- Volume
- 16
- Issue
- S3
- Pages
- S11-22
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC2687326
- OpenAlex
- W2154308320
- Cited by
- 338
- References
- 172
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 16 · 2023: 10 · 2022: 17 · 2021: 18 · 2020: 24 · 2019: 22 · 2018: 23 · 2017: 32 · 2016: 26 · 2015: 29 · 2014: 21 · 2013: 17 · 2012: 23
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071082)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- food intake regulation, physical activity, energy balance, hypothalamus, caudal brainstem, appetite, homeostatic regulation, limbic system, basal ganglia, reward expectancy, food cues, neural circuits, energy expenditure, perinatal programming
- MeSH terms
- Animals, Appetite Regulation, Energy Intake, Energy Metabolism, Humans, Neural Pathways, Obesity
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