Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin
Open accessAbstract
Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation-stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin-induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation-stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation-stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation-stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin-resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator-activated receptor-gamma; an action may contribute to the insulin-sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.
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Dysregulation of adipokines may lead to endocrine diseases.
“As adipokines are involved in many critical physiological processes in the body, dysregulation of adipokines may lead to endocrine diseases (5).”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [5]
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- Authors
- Havel, P. J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Havel, Peter J.
- ORCID
- Havel, Peter J.
- Venue
- Current Opinion in Lipidology
- Published
- 2002-02
- Volume
- 13
- Issue
- 1
- Pages
- 51-59
- ISSN
- 0957-9672 (ISSN-L)
- OpenAlex
- W2068491028
- Cited by
- 575
- References
- 103
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 19 · 2019: 7 · 2018: 11 · 2017: 13 · 2016: 25 · 2015: 28 · 2014: 25 · 2013: 27 · 2012: 28
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- Current Opinion in Lipidology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- leptin, acylation stimulating protein, adiponectin, energy homeostasis, insulin sensitivity, insulin resistance, leptin deficiency, leptin receptor, appetite regulation, adiposity, obesity, hyperlipidemia, lipoatrophy, fat oxidation, chylomicrons, dietary fat, fructose, insulin signaling, PPARγ, triglyceride synthesis
- MeSH terms
- Animals, Blood Proteins, Energy Metabolism, Homeostasis, Humans, Insulin, Proteins, Complement C3a, Adipocytes, Leptin, Intercellular Signaling Peptides and Proteins, Adiponectin
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