Blaming the brain for obesity: integration of hedonic and homeostatic mechanisms
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The brain plays a key role in the controls of energy intake and expenditure, and many genes associated with obesity are expressed in the central nervous system. Technological and conceptual advances in both basic and clinical neurosciences have expanded the traditional view of homeostatic regulation of body weight by mainly the hypothalamus to include hedonic controls of appetite by cortical and subcortical brain areas processing external sensory information, reward, cognition, and executive functions. Hedonic controls interact with homeostatic controls to regulate body weight in a flexible and adaptive manner that takes environmental conditions into account. This new conceptual framework has several important implications for the treatment of obesity. Because much of this interactive neural processing is outside awareness, cognitive restraint in a world of plenty is made difficult and prevention and treatment of obesity should be more rationally directed to the complex and often redundant mechanisms underlying this interaction.
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Weight-loss-induced appetite signals could cause subconscious biases such as gradually increasing portion sizes.
“Thus, signals to the brain that increase appetite with weight loss could introduce subconscious biases such as portion sizes creeping upwards over time.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [37]
In “Set point theory” (page unavailable), the paper says that underfeeding prompts adaptive changes in food intake that return body weight toward its prior level. Its discussion of mindless eating says habitual intake can occur outside awareness. It does not connect weight-loss-induced appetite signals to portion sizes gradually increasing over time. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe perception of ongoing diet maintenance despite no further weight loss may occur because appetite regulation happens in brain regions below conscious awareness.
“The patient’s perception of ongoing diet maintenance despite no further weight loss may arise because the physiological regulation of appetite occurs in brain regions that operate below the patient’s conscious awareness37.”
From Maintenance of Lost Weight and Long-Term Management of Obesity (2018) · cites this paper as [37]
The ‘Neural Control of Appetite and Food Intake’ section (page not provided) says much of the brain’s processing of food intake occurs outside awareness. The Conclusions (page not provided) similarly say homeostatic processes operate outside awareness and that weight loss cannot simply be willed. The paper does not address a patient’s perception of maintaining a diet despite a weight-loss plateau or establish that unconscious appetite regulation explains that perception. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFat and carbohydrates, particularly sweet foods, are robust drivers of food choice and intake, with humans preferring and overconsuming sweet and/or fatty foods due to palatability, pleasure, and reward rather than specific defense of metabolic need.
“Fat and carbohydrates, particularly sweet foods, are robust drivers of food choice and intake, with humans both preferring and overconsuming diets or foods that are sweet and/or fatty, not due to any specific defense of metabolic need, but instead due to palatability, pleasure, and reward”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [1]
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FGF21 and the physiological regulation of macronutrient preference
Hill, C. M., Qualls-Creekmore, E., Berthoud, H.-R., Soto, P., Yu, S., McDougal, D. H., Münzberg, H., & Morrison, C. D. (2020) · Endocrinology · doi:10.1210/endocr/bqaa019 · Cited by 99 · see citing works
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Brain Activity Associated with Breakthrough Food Preoccupation in an Individual on Tirzepatide
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Poghosyan, V., Ioannou, S., Al-Amri, K. M., Al-Mashhadi, S. A., Al-Mohammed, F., Al-Otaibi, T., & Al-Saeed, W. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.948063 · Cited by 8 · see citing works
- Authors
- Berthoud, H.-R., Münzberg, H., & Morrison, C. D.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Berthoud, Hans-Rudolf
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 152
- Issue
- 7
- Pages
- 1728-1738
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC5406238
- OpenAlex
- W2586782237
- Semantic Scholar
- 778203f1405e26ca2f318b87a237dadda587b0bc
- Cited by
- 445
- References
- 88
- Citations by year
- 2026: 39 · 2025: 59 · 2024: 62 · 2023: 47 · 2022: 44 · 2021: 76 · 2020: 51 · 2019: 36 · 2018: 22 · 2017: 8
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Gastroenterology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Institutes of Health (DK 047348, DK081563, DK092587, DK105032)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- obesity, brain, homeostatic regulation, appetite, energy intake, energy expenditure, hypothalamus, reward, executive function, cognitive restraint, obesity treatment, obesity prevention
- MeSH terms
- Self-Control, Animals, Appetite, Body Weight, Brain, Eating, Energy Metabolism, Homeostasis, Humans, Nutritional Status, Obesity, Smell, Taste, Vision, Ocular
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