ESPE Abstracts (2015) 84 P-2-382

Insulin-Like Factor 5 -A Novel Orexigenic Hormone in Humans is Dysregulated in Obesity

Isabel V Wagnera,e, Gesine Flehmigc, Kathrin Scheuermannb, Dennis Löfflerb,e, Antje Körnerb,e, Wieland Kiessb,d, Michael Stumvollc,e, Arne Dietriche, Matthias Blueherc,e, Nora Klötingc,d, Olle Södera & Konstantin Svechnikova


aKarolinska Institute, Stockholm, Sweden; bCenter for Pediatric Research, University Leipzig, Leipzig, Germany; cDepartment of Medicine, Division of Endocrinology, University Hospital Leipzig, Leipzig, Germany; dDepartment of Women’s and Child Health, University Hospital Leipzig, Leipzig, Germany; eIntegrated Research and Treatment Center (IFB Adiposity Diseases), Leipzig, Germany


Background: Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. INSL5 levels are elevated by prolonged calorie restriction and declined with feeding, suggesting that it might be an orexigenic hormone.

Objectives and hypotheses: Our aim was to explore the relationship between INSL5 and different metabolic parameters in lean and obese subjects and to identify possible links between INSL5 and the development of metabolic disorders such as obesity and diabetes.

Methods: INSL5 was measured in serum samples by ELISA. 20 lean and 20 obese females and males were included. 15 morbidly obese patients were tested before and 6 months after they underwent bariatric surgery. We measured INSL5 levels in ten lean and obese individuals after an overnight fasting, after a meal and during an oral glucose tolerance test (OGTT). For all groups, correlations between INSL5 concentrations and anthropometric, metabolic and hormonal measures were investigated.

Results: Serum levels of INSL5 were significantly higher (by 25.5%, P<0.05) in lean females compared to lean males. This gender specific difference was not observed in obese subjects. Basal INSL5 was significantly lower in the obese group (by 28.6%, P<0.05). Levels of INSL5 were negatively correlated to testosterone in lean and obese males and positively to insulin and glucose in both genders. After bariatric surgery males lost 25% of their body weight, increased their testosterone levels (by 97%) and reduced INSL5 levels (by 17.4%). Obese subjects with type 2 diabetes (T2DM) had lower INSL5 before and after surgery compared to obese persons without T2DM. Food consumption decreased INSL5 levels in lean females (by 21.8%) and males (by 20.8%), while interestingly this effect was not observed in obese individuals of both genders.

Conclusion: The fact that the gender-related difference in INSL5 was observed only in lean individuals suggests that INSL5 regulation is dependent on the metabolic state. Negative influence of insulin resistance and T2DM on INSL5 in obese individuals may indicate a link between beta cell function and INSL5 regulation. Therefore, INSL5 may become an interesting target for the development of new therapeutic agents to treat metabolic disorders.

Funding: ESPE Research Fellowship.