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المؤلفMunusamy, Shankar
المؤلفdo Carmo, Jussara M.
المؤلفHosler, Jonathan P.
المؤلفHall, John E.
تاريخ الإتاحة2016-11-07T07:31:48Z
تاريخ النشر2015-10-15
اسم المنشورAJP - Renal Physiology
المعرّفhttp://dx.doi.org/10.1152/ajprenal.00188.2015
الاقتباسMunusamy S, do Carmo JM, Hosler JP, Hall JE. Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin. American Journal of Physiology - Renal Physiology. 2015;309(8):F731-F743.
الرقم المعياري الدولي للكتاب1931-857X
معرّف المصادر الموحدhttp://hdl.handle.net/10576/4976
الملخصWe investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R−/−), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R−/− mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R−/− mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R−/− mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin.
راعي المشروعNational Heart, Lung, and Blood Institute Grant (PO1HL51971), the National Institute of General Medical Sciences (P20GM104357), and an American Heart Association (Greater Southeast Affiliate) Postdoctoral Fellowship Grant (09POST2300079) to S. Munusamy and a Scientist Development Grant (AHA58161) to J. M. do Carmo.
اللغةen
الناشرAmerican Physiological Society
الموضوعendoplasmic reticulum stress
kidney
leptin
melanocortin-4 receptor (MC4R)
mitochondria
nephropathy
obesity
العنوانObesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin
النوعArticle
رقم العدد8
رقم المجلد309
dc.accessType Abstract Only


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