Endocrinology 2013 Sep 3;154(9):3366-76. Epub 2013 Jul 3.

Department of Internal Medicine, Wonkwang University, Gunpo 570–479, South Korea.

Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.

Download full-text PDF

Source
http://dx.doi.org/10.1210/en.2012-2276DOI Listing
September 2013
3 Reads

Publication Analysis

Top Keywords

db/db mice
12
fgf21
12
insulin resistance
12
renal injury
8
growth factor
8
cells fgf21
8
fgf21 receptor
8
fibroblast growth
8
mesangial cells
8
fgf21 treatment
8
type diabetic
8
improves insulin
8
diabetic nephropathy
8
receptor components
8
renal
5
suggests fgf21-resistant
4
fgf21-resistant state
4
treatment down-regulated
4
state fgf21
4
down-regulated fgf21
4

Altmetric Statistics

Similar Publications

Pharmacological efficacy of FGF21 analogue, liraglutide and insulin glargine in treatment of type 2 diabetes.

J Diabetes Complications 2017 Apr 21;31(4):726-734. Epub 2017 Jan 21.

College of Life Science, Northeast Agricultural University, No. 59 Mucai Street, 150030, Harbin, Heilongjiang Province, China. Electronic address:

Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. Read More

View Article
April 2017

CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice.

Kidney Int 2010 Nov 4;78(9):883-94. Epub 2010 Aug 4.

Division of Nephrology, Department of Internal Medicine, Korea University, Ansan City, Korea.

Chemokine ligand 2 (CCL2) binds to its receptor C-C chemokine receptor 2 (CCR2), initiating tissue inflammation, and recent studies have suggested a beneficial effect of a blockade of this pathway in diabetic nephropathy. To investigate the mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on insulin resistance and diabetic nephropathy in db/db mice. Administering this antagonist improved insulin resistance as confirmed by various biomarkers, including homeostasis model assessment index levels, plasma insulin levels, and lipid abnormalities. Read More

View Article
November 2010

Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice.

Endocrinology 2012 Mar 10;153(3):1387-96. Epub 2012 Jan 10.

Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, 425-020, Korea.

The endocannabinoid system is important in the pathogenesis of obesity-related metabolic disorders. However, the effect of inhibiting the endocannabinoid system in type 2 diabetic nephropathy is unclear. Therefore, we examined the effect of the cannabinoid (CB)1 receptor antagonist, SR141716, on insulin resistance and diabetic nephropathy in db/db mice. Read More

View Article
March 2012

Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance.

Endocrinology 2012 Jan 8;153(1):69-80. Epub 2011 Nov 8.

Department of Metabolic Disorders, Amgen Inc., MS 29-1-A, One Amgen Center Drive, Thousand Oaks, California 91320, USA.

Circulating levels of fibroblast growth factor 21 (FGF21), a metabolic regulator of glucose, lipid, and energy homeostasis, are elevated in obese diabetic subjects, raising questions about potential FGF21 resistance. Here we report tissue expression changes in FGF21 and its receptor components, and we describe the target-organ and whole-body responses to FGF21 in ob/ob and diet-induced obese (DIO) mice. Plasma FGF21 concentrations were elevated 8- and 16-fold in DIO and ob/ob mice, respectively, paralleling a dramatic increase in hepatic FGF21 mRNA expression. Read More

View Article
January 2012