Caloric restriction improves glucose homeostasis, yet increases cardiometabolic risk in caveolin-1-deficient mice
| Autor: | Gordon H. Williams, Tsuyoshi Homma, Mika Homma, Jose R. Romero, Amanda E Garza, Gail K. Adler, Nurul Hasanah, Isis Katayama Rangel, Luminita H. Pojoga, Korapat Mayurasakorn |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Caveolin 1 Blood Pressure 030204 cardiovascular system & hematology Renin-Angiotensin System 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Insulin resistance Weight loss Risk Factors Internal medicine Diabetes mellitus Medicine Glucose homeostasis Animals Homeostasis Caloric Restriction Metabolic Syndrome Mice Knockout Aldosterone business.industry Insulin medicine.disease 030104 developmental biology chemistry Cardiovascular Diseases cardiovascular system medicine.symptom Metabolic syndrome Insulin Resistance business |
| Zdroj: | Metabolism: clinical and experimental. 83 |
| ISSN: | 1532-8600 |
| Popis: | Background and Purpose The plasma membrane protein caveolin-1 (CAV-1) has been shown to be involved in modulating glucose homeostasis and the actions of the renin-angiotensin-aldosterone system (RAAS). Caloric restriction (CR) is widely accepted as an effective therapeutic approach to improve insulin sensitivity and reduce the severity of diabetes. Recent data indicate that polymorphisms of the CAV-1 gene are strongly associated with insulin resistance, hypertension and metabolic abnormalities in non-obese individuals. Therefore, we sought to determine whether CR improves the metabolic and cardiovascular (CV) risk factors in the lean CAV-1 KO mice. Materials/Methods Twelve- to fourteen-week-old CAV-1 knockout (KO) and genetically matched wild-type (WT) male mice were randomized by genotype to one of two dietary regimens: ad libitum (ad lib) food intake or 40% CR for 4 weeks. Three weeks following the onset of dietary restriction, all groups were assessed for insulin sensitivity. At the end of the study, all groups were assessed for fasting glucose, insulin, HOMA-IR, lipids, corticosterone levels and blood pressure (BP). Aldosterone secretion was determined from acutely isolated Zona Glomerulosa cells. Results We confirmed that the CAV-1 KO mice on the ad lib diet display a phenotype consistent with the cardiometabolic syndrome, as shown by higher systolic BP (SBP), plasma glucose, HOMA-IR and aldosterone levels despite lower body weight compared with WT mice on the ad lib diet. CAV-1 KO mice maintained their body weight on the ad lib diet, but had substantially greater weight loss with CR, as compared to caloric restricted WT mice. CR-mediated changes in weight were associated with dramatic improvements in glucose and insulin tolerance in both genotypes. These responses to CR, however, were more robust in CAV-1KO vs. WT mice and were accompanied by reductions in plasma glucose, insulin and HOMA-IR in CAV-1KO but not WT mice. Surprisingly, in the CAV-1 KO, but not in WT mice, CR was associated with increased SBP and aldosterone levels, suggesting that in CAV-1 KO mice CR induced an increase in some CV risk factors. Conclusions CR improved the metabolic phenotype in CAV-1 KO mice by increasing insulin sensitivity; nevertheless, this intervention also increased CV risk by inappropriate adaptive responses in the RAAS and BP. |
| Databáze: | OpenAIRE |
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