Body weight control by a high-carbohydrate/low-fat diet slows the progression of diabetic kidney damage in an obese, hypertensive, type 2 diabetic rat model

Abstract

Obesity is one of several factors implicated in the genesis of diabetic nephropathy (DN). Obese, hypertensive, type 2 diabetic rats SHR/NDmcr-cp were given, for 12 weeks, either a normal, middle-carbohydrate/middle-fat diet (MC/MF group) or a high-carbohydrate/low-fat diet (HC/LF group). Daily caloric intake was the same in both groups. Nevertheless, the HC/LF group gained less weight. Despite equivalent degrees of hypertension, hyperglycemia, hyperlipidemia, hyperinsulinemia, and even a poorer glycemic control, the HC/LF group had less severe renal histological abnormalities and a reduced intrarenal advanced glycation and oxidative stress. Mediators of the renoprotection, specifically linked to obesity and body weight control, include a reduced renal inflammation and TGF-beta expression, together with an enhanced level of adiponectin. Altogether, these data identify a specific role of body weight control by a high-carbohydrate/low-fat diet in the progression of DN. Body weight control thus impacts on local intrarenal advanced glycation and oxidative stress through inflammation and adiponectin levels.

Figure 1

Daily diet intake. (a) Daily calorie intake, (b) carbohydrate intake, (c) fat intake, (d) protein intake, and (e) sodium intake in MC/MF (closed square) and HC/LF (open square). **P < .01, ***P < .001 versus MC/MF.

Figure 2

Metabolic abnormalities. (a) Body weight, (b) HbA1c, (c) triglycerides, (d) insulin, and (d) systolic blood pressure. WKY (closed triangle), MC/MF (closed square), and HC/LF (open square). *P < .05, **P < .01, ***P < .001 versus WKY; ^††P < .01, ^†††P < .001 versus MC/MF.

Figure 3

Changes of proteinuria. WKY (closed triangle), MC/MF (closed square), and HC/LF (open square). **P < .01, ***P < .001 versus WKY; ^†††P < .001 versus MC/MF.

Figure 4

Glomerular sclerosis, tubulointerstitial fibrosis, and macrophage infiltration. PAS-stained (a)–(c), Masson trichrome-stained (d)–(f), or ED-1-immunostained (g) and (h) renal tissues. WKY rats (a), (d), MC/MF (c), (f), (h), and HC/LF (b), (e), (g) at the end of study. Arrows indicate ED-1 positive cells. Original magnification 400× ((a)–(c), (g), (h)) and 200× (d)–(f).

Figure 5

Inflammation in renal tissues. (a) ED-1 positive cells in tubulointerstitial area, (b) gene expressions of TNF-alpha, ICAM-1, and VCAM-1, and (c) plasma adiponectin level in MC/MF (white bar) and HC/LF (black bar). *P < .05, **P < .01.

Figure 6

TGF-beta in renal tissues and its induction in vitro by TNF-alpha. (a) Gene expressions of TGF-beta, CTGF, and PAI-1 in MC/MF (white bar) and HC/LF (black bar).*P < .05, **P < .01. (b) Effects of TNF-alpha on TGF-beta mRNA expressions in vitro in cultured rat proximal tubular cells (IRPTC). *P < .05, **P < .01.

Figure 7

Advanced glycation and oxidative stress in renal tissues. (a) Renal pentosidine content, and (b) gene expressions of Nox2 and p47^phox in MC/MF (white bar) and HC/LF (black bar).*P < .05, **P < .01.