Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Abstract
The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob / ob mice. Plasma levels of this protein were increased in diabetic ( db ) mice, a mutant thought to be resistant to the effects of ob . Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob / ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db / db mice. The protein reduced food intake and increased energy expenditure in ob / ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.
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Among the most often used genetic models of MASLD are mice deficient for leptin (ob/ob) or the leptin receptor (db/db).
“Among the most often used genetic models of MASLD are mice genetically deficient for leptin (ob/ob) or the leptin receptor (db/db) (216-219).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [217]
The gene is disrupted in the 2 available alleles of ob; in the original C57/Bl6J ob/ob mutation, a nonsense mutation disrupts protein function, whereas in the second coisogenic ob 2j mutation, a retroviral insertion abrogrates expression of the coding sequence altogether.
“The gene is disrupted in the 2 available alleles of ob; in the original C57/Bl6J ob/ob mutation, a nonsense mutation disrupts protein function, whereas in the second coisogenic ob 2j mutation, a retroviral insertion abrogrates expression of the coding sequence altogether (2,21).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [2]
The failure of recombinant leptin to alter food intake or weight in db mice established the specificity of the effect and essentially excluded the possibility that the protein reduced weight as a result of an aversive effect.
“The failure of recombinant leptin to alter food intake or weight in db mice established the specificity of the effect and essentially excluded the possibility that the protein reduced weight as a result of an aversive effect (2).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [2]
Leptin circulates in the plasma of all mammals tested, including humans and rodents, as an '16-kD protein with a single disulfide bond that is required for bioactivity.
“Leptin circulates in the plasma of all mammals tested, including humans and rodents, as an '16-kD protein with a single disulfide bond that is required for bioactivity (2).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [2]
Infusions of low-dose leptin centrally replicate all the effects of peripheral leptin even at intracerebroventricular doses that do not alter plasma leptin concentrations.
“infusions of low-dose leptin centrally replicate all the effects of peripheral leptin even at intracerebroventricular doses that do not alter plasma leptin concentrations (2).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [2]
Administration of leptin or insulin into the brain reduces food intake and body weight.
“Administration of either peptide into the brain reduces food intake and body weight (30, 76, 200)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [76]
ob/ob mice are more sensitive to leptin than normal mice.
“despite clear evidence that ob/ob mice are more sensitive to leptin than normal mice (30, 76).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [76]
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“leptin-infused ob/ob mice are fundamentally indistinguishable where leptin sensitivity and energy homeostasis are concerned, despite clear evidence that ob/ob mice are more sensitive to leptin than normal mice (30, 76).”
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- Authors
- Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Rockefeller University (US)
- Columbia University (US)
- Brookwood Biomedical Center, Birmingham, AL 35209, USA.
- Venue
- Science
- Published
- 1995-07-28
- Volume
- 269
- Issue
- 5223
- Pages
- 543-546
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2014093920
- Cited by
- 4,451
- References
- 10
- Citations by year
- 2026: 28 · 2025: 32 · 2024: 50 · 2023: 39 · 2022: 68 · 2021: 104 · 2020: 73 · 2019: 115 · 2018: 84 · 2017: 100 · 2016: 121 · 2015: 112 · 2014: 167 · 2013: 142 · 2012: 158
- FWCI
- 105.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-41096, R01DK041096)
- National Center for Research Resources (RR00862, P41RR000862)
- 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
- obese gene, leptin, ob/ob mice, db/db mice, body weight regulation, weight loss, dietary intake, energy expenditure, fat mass, plasma leptin, diabetes mellitus
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Composition, Diabetes Mellitus, Eating, Energy Metabolism, Female, Humans, Mice, Inbred C57BL, Mice, Obese, Obesity, Proteins, Recombinant Proteins, Weight Loss, Leptin, Mice
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