Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet‐induced obesity
Open accessAbstract
Objective: Microarray studies identified Ch12:orf39 (Spexin) as the most down‐regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis. Methods: Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet‐induced obesity (DIO). Its effects on adipocyte [ 3 H]‐oleate uptake were determined. Results: In humans, Spexin gene expression was down‐regulated 14.9‐fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating ( r = −0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects. Conclusions: Spexin gene expression is markedly down‐regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.
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C12orf39 (Spexin) is associated with weight regulation.
“C12orf39 (Spexin), with the latter associated with weight regulation38.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [38]
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Oxytocin pathway gene networks in the human brain
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- Authors
- Walewski, J. L., Ge, F., Lobdell, H., Levin, N., Schwartz, G. J., Vasselli, J. R., Pomp, A., Dakin, G., & Berk, P. D.
- Affiliations
- Columbia University Irving Medical Center (US)
- CovX Pharmaceuticals San Diego California 92121 USA
- Albert Einstein College of Medicine (US)
- St. Luke's-Roosevelt Hospital Center (US)
- Weill Cornell Medical Center (US)
- Corresponding author
- Berk, Paul D.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2014-03-08
- Volume
- 22
- Issue
- 7
- Pages
- 1643-1652
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC4077920
- OpenAlex
- W1913890968
- Cited by
- 196
- References
- 37
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 17 · 2023: 18 · 2022: 25 · 2021: 30 · 2020: 20 · 2019: 21 · 2018: 16 · 2017: 7 · 2016: 9 · 2015: 4
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Obesity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DK-66667, DK-52401, DK-72526,DK072526-04eS1)
- 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
- spexin, diet-induced obesity, oleate uptake, weight loss, appetite regulation, energy homeostasis, respiratory exchange ratio, leptin, obesity treatment, adipose tissue gene expression
- MeSH terms
- Animals, Body Weight, Energy Intake, Eating, Fatty Acids, Feeding Behavior, Humans, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Weight Loss, Down-Regulation, Rats, Wistar, Adipocytes, Oleic Acid, Leptin, Peptide Hormones, Protein Array Analysis, Mice, Rats
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