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Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice.

ABSTRACT: Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations.Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks.In HF/HC-fed mice, HRP increased the expression of several enzymes implicated in lipogenesis and lipolysis in subcutaneous fat (SCF) while the expression of the enzyme implicated in the last step of lipogenesis decreased in VAT. A reduction was also observed in circulating free fatty acids in these animals which was accompanied by normalized adipocyte size in VAT and increased adipocyte size in SCF. ''Beiging'' is the evolution of a white adipose tissue toward a brown-like phenotype characterized by an increased mitochondrial density and small lipid droplets. HRP increased the expression of' "beiging" markers in SCF of HF/HC diet-fed mice.HRP treatment may favor healthy fat storage in SCF by activating a triglyceride/free fatty acid cycling and "beiging," which could explain the body weight and fat mass reduction.

SUBMITTER: Tan P

PROVIDER: S-EPMC5080620 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice.

Tan Paul P Blais Carolane C Nguyen Thi M-D TM Schiller Peter W PW Gutkowska Jolanta J Lavoie Julie L JL

Obesity (Silver Spring, Md.) 20160726 9

<h4>Objective</h4>Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations.<h4>Methods</h4>Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks.<h4>Results</h4>In HF/HC-fed mice, HRP increased the expression of several enzymes implicate ...[more]

PMID: 27458124

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Project description:IntroductionProrenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD.MethodsWe evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics.ResultsA total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively.Discussion/conclusionsThe cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.

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Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice.

Publications

Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice.

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