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The impact of reduced kidney mass on adipose tissue metabolism and whole-body glucose homeostasis in mice


Chin, Siew Hung. The impact of reduced kidney mass on adipose tissue metabolism and whole-body glucose homeostasis in mice. 2014, University of Zurich, Faculty of Science.

Abstract

Reduced kidney mass by uninephrectomy may result in multiple metabolic derangements, including insulin resistance. In this regard, using the ‘gold standard’ hyperinsulinaemic-euglycaemic clamp technique, DeFronzo et al. found evidence of reduced insulin responsiveness in peripheral tissues of chronic kidney disease (CKD) patients, most likely in skeletal muscle tissues. However, the underlying mechanisms still remain unclear. The principal goal of the present project was to determine the impact of reduced kidney mass on glucose metabolism in lean and obese mice. To this end, male C57BL6/J mice underwent uninephrectomy (UniNx) or sham operation at 7 weeks of age. After surgery, animals were fed either chow (standard) or high fat diet (HFD). Glucose homeostasis was assessed 2, 8 and 20 weeks after surgery. No significant differences were observed in glucose tolerance between sham-operated and UniNx mice. However, skeletal muscle insulin resistance as assessed by hyperinsulinaemic-euglycaemic clamp was significantly deteriorated in HFD-fed UniNx mice, whereas insulin-stimulated glucose uptake into isolated skeletal muscle was similar between HFD-fed sham-operated and UniNx mice. Importantly, capillary density was significantly reduced in skeletal muscle of HFD-fed UniNx mice. In contrast, hepatic insulin sensitivity was improved and HFD-induced adipose tissue inflammation was reduced in UniNx mice. Moreover, expression of hypoxia inducible factor 1-alpha (HIF1a) was reduced in adipose tissue of HFD-fed UniNx mice. However, treatment with the angiotensin II type I receptor blocker i.e. telmisartan improved glucose tolerance and hepatic insulin sensitivity only in HFD-fed sham-operated mice but not HFD-fed UniNx mice. In conclusion, UniNx protects from obesity-induced adipose tissue inflammation and hepatic insulin resistance potentially via a reduction in HIF1a expression. In contrast, UniNx reduces muscle capillary density, and thus deteriorates HFD-induced skeletal muscle glucose disposal in vivo.

Reduced kidney mass by uninephrectomy may result in multiple metabolic derangements, including insulin resistance. In this regard, using the ‘gold standard’ hyperinsulinaemic-euglycaemic clamp technique, DeFronzo et al. found evidence of reduced insulin responsiveness in peripheral tissues of chronic kidney disease (CKD) patients, most likely in skeletal muscle tissues. However, the underlying mechanisms still remain unclear. The principal goal of the present project was to determine the impact of reduced kidney mass on glucose metabolism in lean and obese mice. To this end, male C57BL6/J mice underwent uninephrectomy (UniNx) or sham operation at 7 weeks of age. After surgery, animals were fed either chow (standard) or high fat diet (HFD). Glucose homeostasis was assessed 2, 8 and 20 weeks after surgery. No significant differences were observed in glucose tolerance between sham-operated and UniNx mice. However, skeletal muscle insulin resistance as assessed by hyperinsulinaemic-euglycaemic clamp was significantly deteriorated in HFD-fed UniNx mice, whereas insulin-stimulated glucose uptake into isolated skeletal muscle was similar between HFD-fed sham-operated and UniNx mice. Importantly, capillary density was significantly reduced in skeletal muscle of HFD-fed UniNx mice. In contrast, hepatic insulin sensitivity was improved and HFD-induced adipose tissue inflammation was reduced in UniNx mice. Moreover, expression of hypoxia inducible factor 1-alpha (HIF1a) was reduced in adipose tissue of HFD-fed UniNx mice. However, treatment with the angiotensin II type I receptor blocker i.e. telmisartan improved glucose tolerance and hepatic insulin sensitivity only in HFD-fed sham-operated mice but not HFD-fed UniNx mice. In conclusion, UniNx protects from obesity-induced adipose tissue inflammation and hepatic insulin resistance potentially via a reduction in HIF1a expression. In contrast, UniNx reduces muscle capillary density, and thus deteriorates HFD-induced skeletal muscle glucose disposal in vivo.

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Additional indexing

Item Type:Dissertation
Referees:Verrey François, Konrad Daniel, Baumgartner Matthias R, Langhans Wolfgang
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:20 August 2014
Deposited On:20 Aug 2015 10:31
Last Modified:05 Apr 2016 19:21
Permanent URL: https://doi.org/10.5167/uzh-112333

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