Postnatal administration of leptin antagonist mitigates susceptibility to obesity under high-fat diet in male αMUPA mice
| Autor: | Roee Gutman, Snait Tamir, Danielle Zecharia, Maayan Rauch, Adi Sharabi-Nov |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Leptin medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Diet High-Fat Weight Gain Receptors Urokinase Plasminogen Activator 03 medical and health sciences Eating Mice 0302 clinical medicine Species Specificity Pregnancy Physiology (medical) Internal medicine Hyperinsulinism medicine Animals Obesity business.industry digestive oral and skin physiology Body Weight Antagonist nutritional and metabolic diseases High fat diet medicine.disease 030104 developmental biology Endocrinology Animals Newborn Female Leptin signaling Disease Susceptibility business Energy Metabolism hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 317(5) |
| ISSN: | 1522-1555 |
| Popis: | Perturbations in postnatal leptin signaling have been associated with altered susceptibility to diet-induced obesity (DIO) under high-fat-diet (HFD), albeit with contradicting evidence. Previous studies have shown that alpha murine urokinase-type plasminogen activator (αMUPA) mice have a higher and longer postnatal leptin surge compared with their wild types (WTs) as well as lower body weight and food intake under regular diet (RD). Here we explored αMUPA's propensity for DIO and the effect of attenuating postnatal leptin signaling with leptin antagonist (LA) on energy homeostasis under both RD and HFD. Four-day-old αMUPA pups were treated on alternate days until postnatal day 18 with either vehicle or LA (10 or 20 mg·day−1·kg−1) and weaned into RD or HFD. Compared with RD-fed αMUPA males, HFD-fed αMUPA males showed higher energy intake, even when corrected for body weight difference, and became hyperinsulinemic and obese. Additionally, HFD-fed αMUPA males gained body weight at a higher rate than their WTs mainly because of strain differences in energy expenditure. LA administration did not affect strain differences under RD but attenuated αMUPA’s hyperinsulinemia and DIO under HFD, most likely by mediating energy expenditure. Together with our previous findings, these results suggest that αMUPA’s leptin surge underlies its higher susceptibility to obesity under HFD, highlighting the role of leptin-related developmental processes in inducing obesity in a postweaning obesogenic environment, at least in αMUPA males. This study therefore supports the use of αMUPA mice for elucidating developmental mechanisms of obesity and the efficacy of early-life manipulations via leptin surge axis in attenuating DIO. |
| Databáze: | OpenAIRE |
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