Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action
Abstract
The regulation of body weight and composition involves input from genes and the environment, demonstrated, for example, by the variable susceptibility of inbred strains of mice to obesity when offered a high-fat diet. The identification of the gene responsible for obesity in the ob/ob mouse provides a new approach to defining links between diet and genetics in the regulation of body weight. The ob gene protein product, leptin, is an adipocyte-derived circulating protein. Administration of recombinant leptin reduces food intake and increases energy expenditure in ob/ob mice, suggesting that it signals to the brain the magnitude of fat stores. Information on the regulation of this protein is limited. In several rodent models of obesity including db/db, fa/fa, yellow (Ay/a) VMH-lesioned, and those induced by gold thioglucose, monosodium glutamate, and transgenic ablation of brown adipose tissue, leptin mRNA expression and the level of circulating leptin are increased, suggesting resistance to one or more of its actions. We have assessed the impact of increased dietary fat on circulating leptin levels in normal FVB mice and FVB mice with transgene-induced ablation of brown adipose tissue. We find that high-fat diet evokes a sustained increase in circulating leptin in both normal and transgenic mice, with leptin levels accurately reflecting the amount of body lipid across a broad range of body fat. However, despite increased leptin levels, animals fed a high-fat diet became obese without decreasing their caloric intake, suggesting that a high content of dietary fat changes the 'set point' for body weight, at least in part by limiting the action of leptin.
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Leptin is secreted by white adipocytes proportionally to TG stores.
“Leptin is secreted by white adipocytes proportionally to TG stores 35, 36, 37.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [35]
Most humans with obesity, as well as DIO mice fed highly caloric palatable diets, develop insulin resistance and exhibit high plasma levels of leptin.
“Most humans with obesity, as well as DIO mice, fed highly caloric palatable diets, develop insulin resistance, and exhibit high plasma levels of leptin 35.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [35]
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- Authors
- Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Venue
- Nature Medicine
- Published
- 1995-12
- Volume
- 1
- Issue
- 12
- Pages
- 1311-1314
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2087133453
- Cited by
- 1,660
- References
- 20
- Citations by year
- 2026: 10 · 2025: 37 · 2024: 40 · 2023: 37 · 2022: 37 · 2021: 70 · 2020: 52 · 2019: 52 · 2018: 63 · 2017: 42 · 2016: 67 · 2015: 62 · 2014: 65 · 2013: 57 · 2012: 63
- FWCI
- 25.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK43051, P30DK046200, P30 DK-46200, R37DK028082, R01DK043051, R37 DK 28082)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- leptin, high-fat diet, obesity, fat mass, leptin resistance, brown adipose tissue, FVB mice, body weight set point, energy balance, energy intake, ob/ob mice, db/db mice, leptin mRNA expression
- MeSH terms
- Amino Acid Sequence, Animals, Body Weight, Dietary Fats, Female, Male, Mice, Transgenic, Molecular Sequence Data, Obesity, Proteins, Leptin, Lipid Metabolism, Mice
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