Renin-angiotensin system activation in renal adipogenesis.
The kidney is one of the major organs involved in whole-body homeostasis while chronic renal impairment usually leads to fat redistribution and hyperlipidemia. The aim of this study was to elucidate the role of tissue renal renin-angiotensin system (RAS) components, lipogenic peroxisome proliferator-activated receptor-gamma (PPARgamma), and cytokine TNF-alpha in the development of ectopic adipogenesis and lipid deposition. Adult male Sprague-Dawley rats were randomized into three groups: untreated uninephrectomized (UNX) rats, UNX rats treated with an angiotensin-converting enzyme inhibitor (ACEI), lisinopril, and sham-operated rats. All animals were euthanized at 10 mo postoperation. The untreated UNX rats showed increased protein expression of renin, angiotensinogen, PPARgamma, and the angiotensin II type 2 receptor (AT2R) but reduced protein expression of AT1R and TNF-alpha in their remnant kidneys. Immunofluorescence staining revealed increased reactivity of angiotensinogen and angiotensin I/II in renal tubular cells and adipocytes of the untreated UNX rats. ACEI treatment largely prevented these disorders in association with restored normolipidemia and normalized renal adipogenesis and lipid deposition. These findings support the notion that tissue RAS, PPARgamma, and TNF-alpha collectively play an important role in the renal adipogenesis and lipid metabolism.
Sui
Yi
Y
Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China. suiyi@cuhk.edu.hk
Zhao
Hai-Lu
HL
Fan
Rong-Rong
RR
Guan
Jing
J
He
Lan
L
Lee
Heung Man
HM
Chan
Juliana C N
JC
Tong
Peter C Y
PC
D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000473:pathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D006946:Hyperinsulinism; D006949:Hyperlipidemias; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D007672:Kidney Cortex / Q000473:pathology; D050356:Lipid Metabolism / Q000502:physiology; D017706:Lisinopril / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; D017706:Lisinopril