Impact of Dietary Sodium Reduction on the Development of Obesity and
                    Type 2 Diabetes in db/db Mice

Anja Hofmann; Coy Brunssen; Mirko Peitzsch; Jennifer Mittag; Annika Frenzel; Graeme Eisenhofer; Nicholas F. Brown; Steven M. Weldon; Christian Reeps; Stefan R. Bornstein; Henning Morawietz

doi:10.1055/a-1625-6296

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2021; 53(10): 699-704
DOI: 10.1055/a-1625-6296

Endocrine Research

Impact of Dietary Sodium Reduction on the Development of Obesity and Type 2 Diabetes in db/db Mice

Anja Hofmann

¹Division of Vascular Endothelium and Microcirculation, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

²Division of Vascular and Endovascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Coy Brunssen

¹Division of Vascular Endothelium and Microcirculation, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Mirko Peitzsch

³Institute of Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

,

Jennifer Mittag

¹Division of Vascular Endothelium and Microcirculation, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Annika Frenzel

¹Division of Vascular Endothelium and Microcirculation, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Graeme Eisenhofer

³Institute of Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

⁴Department of Medicine III, University Hospital and Faculty of Medicine Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

,

Nicholas F. Brown

⁵Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

,

Steven M. Weldon

⁵Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

,

Christian Reeps

²Division of Vascular and Endovascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

,

Stefan R. Bornstein

⁴Department of Medicine III, University Hospital and Faculty of Medicine Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

⁶Endocrinology and Diabetes, Faculty of Life Sciences & Medicine, Kings College London, London, UK

,

Henning Morawietz

¹Division of Vascular Endothelium and Microcirculation, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

› Institutsangaben

Abstract

The impact of dietary sodium reduction on mouse models of type 2 diabetes is not well understood. Therefore, we analyzed the effect of a low-salt diet on obesity and parameters of type 2 diabetes in db/db mice. Five-week-old male db/db and lean db/m mice were fed a normal salt (0.19% Na⁺, NS) or a low-salt diet (<0.03% Na⁺, LS) for 5 weeks. Body and organ weight and parameters of glucose and insulin tolerance were analyzed. Plasma levels of steroids were determined by liquid chromatography tandem mass spectrometry. Body weight, glucose, and insulin tolerance were not affected by LS. The amount of gonadal adipose tissue showed a trend to be increased by LS whereas liver, pancreas, kidney, heart, and adrenal weight remained unaffected. LS reduced urinary sodium-to-creatinine ratio but did not affect plasma Na⁺ levels in both genotypes. Plasma and urinary potassium-to-creatinine ratio did not differ in all groups of mice. Aldosterone as a major determinant of changes in dietary sodium remained unaffected by LS in db/db mice as well as further investigated steroid hormones. The present study showed reduced sodium-to-creatinine ratio, but no additional effects of dietary sodium reduction on major metabolic parameters and steroid levels in obese and hyper-glycemic db/db mice.

Key words

adipose tissue - aldosterone - diabetes - insulin tolerance - sodium - steroids

Volltext

Referenzen

References
1 Hulthen L, Aurell M, Klingberg S. et al Salt intake in young Swedish men. Public Health Nutr 2010; 13: 601-605
2 Hoffmann IS, Cubeddu LX. Salt and the metabolic syndrome. Nutr Metab Cardiovasc Dis 2009; 19: 123-128
3 He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ 2013; 346: f1325
4 Garg R, Sun B, Williams J. Effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertension. Hypertension 2014; 64: 1384-1387
5 Prada PO, Coelho MS, Zecchin HG. et al Low salt intake modulates insulin signaling, JNK activity and IRS-1ser307 phosphorylation in rat tissues. J Endocrinol 2005; 185: 429-437
6 Coelho MS, Passadore MD, Gasparetti AL. et al High- or low-salt diet from weaning to adulthood: effect on body weight, food intake and energy balance in rats. Nutr Metab Cardiovasc Dis 2006; 16: 148-155
7 Garg R, Williams GH, Hurwitz S. et al Low-salt diet increases insulin resistance in healthy subjects. Metabolism 2011; 60: 965-968
8 Sharma AM, Ruland K, Spies KP. et al Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose. J Hypertens 1991; 9: 329-335
9 Prada P, Okamoto MM, Furukawa LN. et al High- or low-salt diet from weaning to adulthood: effect on insulin sensitivity in Wistar rats. Hypertension 2000; 35: 424-429
10 Hattori T, Murase T, Takatsu M. et al Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome. J Am Heart Assoc 2014; 3: e001312
11 Baudrand R, Lian CG, Lian BQ. et al Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity. Nutr Metab Cardiovasc Dis 2014; 24: 34-41
12 Schweda F. Salt feedback on the renin-angiotensin-aldosterone system. Pflugers Arch 2015; 467: 565-576
13 Luther JM, Brown NJ. The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci 2011; 32: 734-739
14 Hofmann A, Peitzsch M, Brunssen C. et al Elevated steroid hormone production in the db/db mouse model of obesity and type 2 diabetes. Horm Metab Res 2017; 49: 43-49
15 Brunssen C, Hofmann A, Peitzsch M. et al Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells. Horm Metab Res 2017; 49: 701-706
16 Hofmann A, Brunssen C, Peitzsch M. et al Aldosterone synthase inhibition improves glucose tolerance in zucker diabetic fatty (ZDF) rats. Endocrinology 2016; 157: 3844-3855
17 Hofmann A, Brunssen C, Peitzsch M. et al The aldosterone synthase inhibitor FAD286 is suitable for lowering aldosterone levels in ZDF rats but not in db/db mice. Horm Metab Res 2017; 49: 466-471
18 Bovee DM, Visser WJ, Middel I. et al A randomized trial of distal diuretics versus dietary sodium restriction for hypertension in chronic kidney disease. J Am Soc Nephrol 2020; 31: 650-662
19 Peitzsch M, Dekkers T, Haase M. et al An LC-MS/MS method for steroid profiling during adrenal venous sampling for investigation of primary aldosteronism. J Steroid Biochem Mol Biol 2015; 145: 75-84
20 Nishida H, Sohara E, Nomura N. et al Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice. Hypertension 2012; 60: 981-990
21 Coleman DL. Diabetes-obesity syndromes in mice. Diabetes 1982; 31: 1-6
22 Meneton P, Jeunemaitre X, de Wardener HE. et al Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 2005; 85: 679-715
23 Wang Q, Hummler E, Maillard M. et al Compensatory up-regulation of angiotensin II subtype 1 receptors in alpha ENaC knockout heterozygous mice. Kidney Int 2001; 59: 2216-2221
24 Raz-Pasteur A, Gamliel-Lazarovich A, Gantman A. et al Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice. J Renin Angiotensin Aldosterone Syst 2014; 15: 228-235
25 Makhanova N, Sequeira-Lopez ML, Gomez RA. et al Disturbed homeostasis in sodium-restricted mice heterozygous and homozygous for aldosterone synthase gene disruption. Hypertension 2006; 48: 1151-1159
26 Catanozi S, Rocha JC, Nakandakare ER. et al The rise of the plasma lipid concentration elicited by dietary sodium chloride restriction in Wistar rats is due to an impairment of the plasma triacylglycerol removal rate. Atherosclerosis 2001; 158: 81-86
27 Clark JL, Rech L, Chaity N. et al Possible deleterious hormonal changes associated with low-sodium diets. Nutr Rev 2015; 73: 22-35