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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
Author(s) -
Walewski José L.,
Ge Fengxia,
Lobdell Harrison,
Levin Nancy,
Schwartz Gary J.,
Vasselli Joseph R.,
Pomp Afons,
Dakin Gregory,
Berk Paul D.
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20725
Subject(s) - endocrinology , medicine , leptin , adipocyte , respiratory exchange ratio , obesity , weight loss , hormone , fatty acid , diet induced obese , appetite , biology , chemistry , adipose tissue , biochemistry , insulin resistance , heart rate , blood pressure
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.