Caloric restriction improves glucose homeostasis, yet increases cardiometabolic risk in caveolin-1-deficient mice.
Caloric restriction improves glucose homeostasis, yet increases cardiometabolic risk in caveolin-1-deficient mice.
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DOI：
10.1016/j.metabol.2018.01.012
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发表时间：
2018-06
影响因子：
9.8
通讯作者：
Pojoga, Luminita H.
中科院分区：
文献类型：
--
作者：
Mayurasakorn, Korapat;Hasanah, Nurul;Homma, Tsuyoshi;Homma, Mika;Rangel, Isis Katayama;Garza, Amanda E.;Romero, Jose R.;Adler, Gail K.;Williams, Gordon H.;Pojoga, Luminita H.
关键词：
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. 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. 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. 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.
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影响因子：
3.7
作者：
Masharani UB;Maddux BA;Li X;Sakkas GK;Mulligan K;Schambelan M;Goldfine ID;Youngren JF
通讯作者：
Youngren JF
影响因子：
4.5
作者：
Levay, Elizabeth A.;Tammer, Amanda H.;Paolini, Antonio G.
通讯作者：
Paolini, Antonio G.
影响因子：
5.4
作者：
Baudrand R;Gupta N;Garza AE;Vaidya A;Leopold JA;Hopkins PN;Jeunemaitre X;Ferri C;Romero JR;Williams J;Loscalzo J;Adler GK;Williams GH;Pojoga LH
通讯作者：
Pojoga LH
DOI：
10.1161/hypertensionaha.114.04233
发表时间：
2015-01
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Garza AE;Rariy CM;Sun B;Williams J;Lasky-Su J;Baudrand R;Yao T;Moize B;Hafiz WM;Romero JR;Adler GK;Ferri C;Hopkins PN;Pojoga LH;Williams GH
通讯作者：
Williams GH
影响因子：
7.7
作者：
Cohen, AW;Schubert, W;Lisanti, MP
通讯作者：
Lisanti, MP