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      Effect of High Fat Loading in Dahl Salt-Sensitive Rats

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          Abstract

          Salt sensitivity of blood pressure (BP) is speculated to be a characteristic in obesity-induced hypertension. To elucidate the influence of obesity on salt-sensitive hypertension, we examined the effect of fat loading on BP, renal damage, and their progression induced by salt excess in Dahl salt-sensitive (S) rats. High fat (HF: 45% fat diet: 8 weeks) diet increased BP with greater weight gain and visceral fat accumulation than low fat (10% fat) diet. In HF-fed rats, plasma glucose, plasma insulin, and urinary catecholamine increased, and urinary protein tended to be elevated. Moreover, excessive salt (8% salt diet: 8 weeks)-induced hypertension and proteinuria was accelerated in HF-fed rats. Therefore, fat loading increased BP in Dahl S rats possibly through insulin-resistance and sympathetic excitation. Moreover, fat loading accelerated salt-induced BP elevation and renal damage, suggesting excessive intake of both fat and salt, such as a civilized diet, exert the synergic harmful effects.

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          Most cited references30

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          Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway.

          Obesity and metabolic syndrome are associated with glomerulosclerosis and proteinuria, but the mechanisms are not known. The purpose of this study was to determine if there is altered renal lipid metabolism and increased expression of sterol regulatory element-binding proteins (SREBPs) in a model of diet-induced obesity. C57BL/6J mice that were fed a high fat, 60 kcal % saturated (lard) fat diet (HFD) developed obesity, hyperglycemia, and hyperinsulinemia compared with those that were fed a low fat, 10 kcal % fat diet (LFD). In contrast, A/J mice were resistant when fed the same diet. C57BL/6J mice with HFD exhibited significantly higher levels of renal SREBP-1 and SREBP-2 expression than those mice with LFD, whereas in A/J mice there were no changes with the same treatment. The increases in SREBP-1 and SREBP-2 expression in C57BL/6J mice resulted in renal accumulation of triglyceride and cholesterol. There were also significant increases in the renal expression of plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), type IV collagen, and fibronectin, resulting in glomerulosclerosis and proteinuria. To determine a role for SREBPs per se in modulating renal lipid metabolism and glomerulosclerosis we performed studies in SREBP-1c(-/-) mice. In contrast to control mice, in the SREBP-1c(-/-) mice with HFD the accumulation of triglyceride was prevented, as well as the increases in PAI-1, VEGF, type IV collagen, and fibronectin expression. Our results therefore suggest that diet-induced obesity causes increased renal lipid accumulation and glomerulosclerosis in C57BL/6J mice via an SREBP-1c-dependent pathway.
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            The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents.

            To clarify the role of sodium intake in the regulation of blood pressure in obese subjects, we measured blood pressure in 60 obese and 18 nonobese adolescents after successive two-week periods of a high-salt diet (greater than 250 mmol of sodium per day) and a low-salt diet (less than 30 mmol per day). When they were changed from a high-salt to a low-salt diet, the obese group had a significantly larger mean change (+/- SE) in mean arterial pressure (-12 +/- 1 mm Hg) than did the nonobese group (+1 +/- 2 mm Hg; P less than 0.001). The variables that best predicted the degree of sodium sensitivity were the fasting plasma insulin level, the plasma aldosterone level while the low-salt diet was being given, the plasma norepinephrine level while the high-salt diet was being given, and the percentage of body weight made up by fat. Fifty-one of the obese adolescents were also studied before and after a 20-week weight-loss program. After the weight-loss program, the 36 subjects who lost more than 1 kg of body weight had a reduced sensitivity of blood pressure to sodium (difference from value during high-salt diet to that during low-salt diet, -1 +/- 1 mm Hg). The blood pressure of the remaining 15 adolescents was still sensitive to sodium intake (-11 +/- 3 mm Hg). These results support the hypothesis that the blood pressure of obese adolescents is sensitive to dietary sodium intake and that this sensitivity may be due to the combined effects of the hyperinsulinemia, hyperaldosteronism, and increased activity of the sympathetic nervous system that are characteristic of obesity.
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              Role of selective leptin resistance in diet-induced obesity hypertension.

              Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. Leptin also increases sympathetic nerve activity (SNA) and blood pressure. We tested the hypothesis that diet-induced obesity is associated with resistance to the metabolic actions of leptin but preservation of its renal SNA and arterial pressure effects, leading to hypertension. Mice were fed a high-fat diet for 10 weeks to induce moderate obesity. The decrease in food intake and body weight induced by intraperitoneal or intracerebroventricular leptin was significantly attenuated in the obese mice. Regional SNA responses to leptin were differentially altered in diet-induced obese mice. Renal SNA response to leptin was preserved, whereas lumbar and brown adipose tissue SNA responses were attenuated in obese mice. Radiotelemetric arterial pressure was approximately 10 mmHg higher in obese mice. Furthermore, the increase in arterial pressure in response to long-term (12 days) leptin treatment was preserved in obese mice. Thus, mice with diet-induced obesity exhibit circulating hyperleptinemia and resistance to the metabolic actions of leptin. However, there is preservation of the renal sympathetic and arterial pressure responses to leptin, which represent a potential mechanism for the adverse cardiovascular consequences of obesity.
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                Author and article information

                Journal
                Clin Exp Hypertens
                lceh
                Clinical and Experimental Hypertension
                Informa Healthcare
                1064-1963
                1525-6006
                27 July 2009
                August 2009
                : 31
                : 5
                : 451-461
                Affiliations
                Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
                Author notes
                Address correspondence to Katsuyuki Ando, Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan; E-mail: katsua-tky@ 123456umin.ac.jp
                Article
                10.1080/10641960902825487
                2730819
                19811354
                8ff7584e-377d-49bb-922c-b1e1bc863bbb
                Copyright © Informa Healthcare USA, Inc.

                This is an open access article distributed under the Supplemental Terms and Conditions for iOpenAccess articles published in Informa Healthcare journals , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 April 2008
                : 22 July 2008
                : 23 July 2008
                Categories
                Article

                Cardiovascular Medicine
                salt sensitivity of blood pressure,obesity,urinary protein,sympathetic nervous system,insulin resistance

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