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

José L. Walewski, Fengxia Ge, Harrison Lobdell IV, Nancy Levin, Gary J. Schwartz, Joseph R. Vasselli, Afons Pomp, Gregory Dakin, Paul D. Berk

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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 [3H]-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.

Original languageEnglish (US)
Pages (from-to)1643-1652
Number of pages10
JournalObesity
Volume22
Issue number7
DOIs
StatePublished - 2014

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Adipocytes
Weight Loss
Rodentia
Fatty Acids
Obesity
Diet
Peptides
Locomotion
Meals
Fats
Reducing Diet
Appetite Regulation
Gene Expression
Subcutaneous Fat
Oleic Acid
Leptin
Energy Intake
Inbred C57BL Mouse
Wistar Rats
Eating

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

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. / Walewski, José L.; Ge, Fengxia; Lobdell IV, Harrison; Levin, Nancy; Schwartz, Gary J.; Vasselli, Joseph R.; Pomp, Afons; Dakin, Gregory; Berk, Paul D.

In: Obesity, Vol. 22, No. 7, 2014, p. 1643-1652.

Research output: Contribution to journalArticle

Walewski, José L. ; Ge, Fengxia ; Lobdell IV, Harrison ; Levin, Nancy ; Schwartz, Gary J. ; Vasselli, Joseph R. ; Pomp, Afons ; Dakin, Gregory ; Berk, Paul D. / 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. In: Obesity. 2014 ; Vol. 22, No. 7. pp. 1643-1652.
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abstract = "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 [3H]-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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N2 - 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 [3H]-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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