Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment
Open accessAbstract
The obesity pandemic can be viewed as a result of an imbalanced reaction to changing environmental factors. Recent research has linked circadian arrhythmicity to obesity and related diseases; however, the underlying mechanisms are still unclear. In this study, we found that high-fat diet (HFD) feeding strikingly promoted daytime rather than nighttime caloric intake in mice, leading to feeding circadian arrhythmicity. Using scheduled feeding with a defined amount of daily HFD intake, we found that an increase in the ratio of daytime to nighttime feeding promoted weight gain, whereas a decrease of this ratio rebalanced energy expenditure to counteract obesity. In identifying the underlying mechanism, we found that hypothalamic release of anorexigenic neuropeptide oxytocin displayed a diurnal rhythm of daytime rise and nighttime decline, which negatively correlated with the diurnal feeding activities of normal chow-fed mice. In contrast, chronic HFD feeding abrogated oxytocin diurnal rhythmicity, primarily by suppressing daytime oxytocin rise. Using pharmacological experiments with hypothalamic injection of oxytocin or oxytocin antagonist, we showed that daytime manipulation of oxytocin can change feeding circadian patterns to reprogram energy expenditure, leading to attenuation or induction of obesity independently of 24-h caloric intake. Also importantly, we found that peripheral injection of oxytocin activated hypothalamic oxytocin neurons to release oxytocin, and exerted metabolic effects similar to central oxytocin injection, thus offering a practical clinical avenue to use oxytocin in obesity control. In conclusion, resting-stage oxytocin release and feeding activity represent a critical circadian mechanism and therapeutic target for obesity.
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Oxytocin reduces food intake in normal-weight rodents and in animals with diet-induced obesity.
“Importantly, oxytocin reduces food intake not only in normal-weight rodents but also in animals with diet-induced obesity (8,12,13)”
From Oxytocin Reduces Reward-Driven Food Intake in Humans (2013) · cites this paper as [13]
Oxytocin induces weight loss in rodents, and this effect may be related to increased energy expenditure and lipolysis in addition to appetite suppression.
“Oxytocin induces weight loss in rodents, and this effect may be related to increased energy expenditure and lipolyis in addition to appetite suppression(6, 7, 8, 9, 10, 11).”
From Oxytocin reduces caloric intake in men (2015) · cites this paper as [10]
Peripheral OXT delivery can exert anti-obesity effects.
“our studies and others showed that peripheral OXT delivery can work to exert anti-obesity effects [15], [16]”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [15]
Peripherally delivered OXT can promote intra-brain release of OXT to induce metabolic actions.
“peripherally delivered OXT can promote the intra-brain release of OXT to induce the metabolic actions [15]”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [15]
Intra-brain action of OXT can lead to reversal of obesity and related glucose and insulin disorders in mouse models.
“our recent research demonstrated that the intra-brain action of OXT can lead to reversal of obesity as well as related glucose and insulin disorders in mouse models [14], [15].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [15]
OXT when peripherally administrated can lead to activation of hypothalamic OXT neurons to induce central OXT release.
“OXT when peripherally administrated can lead to activation of hypothalamic OXT neurons to induce central OXT release [15]”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [15]
OXT can work in the brain to improve the neural regulation of metabolism and thereby counteract obesity and obesity-related metabolic abnormalities in mouse models.
“Our research further demonstrated that OXT can work in the brain to improve the neural regulation of metabolism and thereby counteract obesity and obesity-related metabolic abnormalities in mouse models [14], [15].”
From Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models (2013) · cites this paper as [15]
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- Authors
- Zhang, G., & Cai, D.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Cai, Dongsheng
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2011-11
- Volume
- 301
- Issue
- 5
- Pages
- E1004-E1012
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3214005
- OpenAlex
- W2140750803
- Cited by
- 171
- References
- 55
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 16 · 2023: 7 · 2022: 10 · 2021: 19 · 2020: 10 · 2019: 14 · 2018: 18 · 2017: 17 · 2016: 15 · 2015: 12 · 2014: 12 · 2013: 9 · 2012: 3
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG031774)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078750)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- obesity, circadian rhythm, oxytocin, high-fat diet, energy expenditure, hypothalamus, anorexigenic peptides, diurnal feeding pattern, weight gain
- MeSH terms
- Animals, Body Weight, Energy Intake, Circadian Rhythm, Feeding Behavior, Feeding Methods, Injections, Intraventricular, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Oxytocics, Oxytocin, Rest, Mice
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