Absence of leptin signaling allows fat accretion in cystic fibrosis mice
| Autor: | Aura Perez, Bernadette O. Erokwu, Gavriella Pora, James Poleman, Alexander Rodriguez-Palacios, Mitchell L. Drumm, Ilya Bederman, Kimberly A. Spoonhower, Christopher A Flask, Maureen O’reilly, Michelle Puchowicz |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leptin Male medicine.medical_specialty Cystic Fibrosis Physiology 030209 endocrinology & metabolism Cystic fibrosis Accretion (finance) 03 medical and health sciences Mice 0302 clinical medicine Physiology (medical) Internal medicine Decreased energy medicine Animals Obesity Hepatology Chemistry Lipogenesis Gastroenterology medicine.disease Increased Lipogenesis Mice Inbred C57BL 030104 developmental biology Endocrinology Energy expenditure Adipose Tissue Female Leptin signaling Diet Carbohydrate Loading Signal Transduction Research Article |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 315(5) |
| ISSN: | 1522-1547 |
| Popis: | Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low body-growth phenotype. As low body weight and body mass index strongly correlate with poor lung health and survival of patients with CF, improving energy balance is an important clinical goal (e.g., high-fat diet). CF mouse models also exhibit negative energy balance (growth retardation and high energy expenditure), independent from exocrine pancreatic insufficiency, lung disease, and malnutrition. To improve energy balance through increased caloric intake and reduced energy expenditure, we disrupted leptin signaling by crossing the db/db leptin receptor allele with mice carrying the R117H Cftr mutation. Compared with db/db mice, absence of leptin signaling in CF mice (CF db/db) resulted in delayed and moderate hyperphagia with lower de novo lipogenesis and lipid deposition, producing only moderately obese CF mice. Greater body length was found in db/db mice but not in CF db/db, suggesting CF-dependent effect on bone growth. The db/db genotype resulted in lower energy expenditure regardless of Cftr genotype leading to obesity. Despite the db/db genotype, the CF genotype exhibited high respiratory quotient indicating elevated carbohydrate oxidation, thus limiting carbohydrates for lipogenesis. In summary, db/db-linked hyperphagia, elevated lipogenesis, and morbid obesity were partially suppressed by reduced CFTR activity. CF mice still accrued large amounts of adipose tissue in contrast to mice fed a high-fat diet, thus highlighting the importance of dietary carbohydrates and not simply fat for energy balance in CF.NEW & NOTEWORTHY We show that cystic fibrosis (CF) mice are able to accrue fat under conditions of carbohydrate overfeeding, increased lipogenesis, and decreased energy expenditure, although length was unaffected. High-fat diet feeding failed to improve growth in CF mice. Morbid db/db-like obesity was reduced in CF double-mutant mice by reduced CFTR activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|