Increased Energy Expenditure, Dietary Fat Wasting, and Resistance to Diet-induced Obesity in Mice Lacking Renin

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2007 Dec 7

PMID 18054319

Citations 63

Authors

Nobuyuki Takahashi

Feng Li

Kunjie Hua

Jianbei Deng

Chih-Hong Wang

Robert R Bowers

Timothy J Bartness

Hyung-Suk Kim

Joyce B Harp

Affiliations

Soon will be listed here.

Abstract

An overactive renin-angiotensin system is associated with obesity and the metabolic syndrome. However, the mechanisms behind it are unclear. Cleaving angiotensinogen to angiotensin I by renin is a rate-limiting step of angiotensin II production, but renin is suggested to have angiotensin-independent effects. We generated mice lacking renin (Ren1c) using embryonic stem cells from C57BL/6 mice, a strain prone to diet-induced obesity. Ren1c(-/-) mice are lean, insulin sensitive, and resistant to diet-induced obesity without changes in food intake and physical activity. The lean phenotype is likely due to a higher metabolic rate and gastrointestinal loss of dietary fat. Most of the metabolic changes in Ren1c(-/-) mice were reversed by angiotensin II administration. These results support a role for angiotensin II in the pathogenesis of diet-induced obesity and insulin resistance.

Citing Articles

Resveratrol Relieves Hepatic Steatosis and Enhances the Effects of Atorvastatin in a Mouse Model of NAFLD by Regulating the Renin-Angiotensin System, Oxidative Stress, and Inflammation.

Babaeenezhad E, Farahmandian N, Sotoudeheian M, Dezfoulian O, Askari E, Taghipour N Food Sci Nutr. 2025; 13(3):e70073.

PMID: 40046578 PMC: 11880619. DOI: 10.1002/fsn3.70073.

Angiotensin in the Arcuate: Mechanisms Integrating Cardiometabolic Control: The 2022 COH Mid-Career Award for Research Excellence.

Lawton S, Wagner V, Nakagawa P, Segar J, Sigmund C, Morselli L Hypertension. 2024; 81(11):2209-2217.

PMID: 39315447 PMC: 11483214. DOI: 10.1161/HYPERTENSIONAHA.124.20524.

Altered local RAS in the liver increased the risk of NAFLD in male mouse offspring produced by in vitro fertilization.

Bo L, Wei L, Shi L, Luo C, Gao S, Zhou A BMC Pregnancy Childbirth. 2023; 23(1):345.

PMID: 37173649 PMC: 10176674. DOI: 10.1186/s12884-023-05681-8.

System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy.

Zhu L, Ma M, Zhang L, Wang S, Guo Y, Ling X Pharmaceutics. 2023; 15(3).

PMID: 36986671 PMC: 10051152. DOI: 10.3390/pharmaceutics15030810.

Insulin Elevates ID2 Expression in Trophoblasts and Aggravates Preeclampsia in Obese ASB4-Null Mice.

Kayashima Y, Townley-Tilson W, Vora N, Boggess K, Homeister J, Maeda-Smithies N Int J Mol Sci. 2023; 24(3).

PMID: 36768469 PMC: 9917068. DOI: 10.3390/ijms24032149.

References

Brommage R . Validation and calibration of DEXA body composition in mice. Am J Physiol Endocrinol Metab. 2003; 285(3):E454-9. DOI: 10.1152/ajpendo.00470.2002. View

Chen H, Smith S, Ladha Z, Jensen D, Ferreira L, Pulawa L . Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest. 2002; 109(8):1049-55. PMC: 150948. DOI: 10.1172/JCI14672. View

Scheen A . Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab. 2005; 30(6):487-96. DOI: 10.1016/s1262-3636(07)70146-5. View

Nguyen G . Renin/prorenin receptors. Kidney Int. 2006; 69(9):1503-6. DOI: 10.1038/sj.ki.5000265. View

Sigmund C, Gross K . Structure, expression, and regulation of the murine renin genes. Hypertension. 1991; 18(4):446-57. DOI: 10.1161/01.hyp.18.4.446. View

Tran M, Forget P, Van den Neucker A, Strik J, Van Kreel B, Kuijten R . The acid steatocrit: a much improved method. J Pediatr Gastroenterol Nutr. 1994; 19(3):299-303. DOI: 10.1097/00005176-199410000-00007. View

Kozak L, Ailhaud G, Darimont C, Negrel R . Angiotensin II as a trophic factor of white adipose tissue: stimulation of adipose cell formation. Endocrinology. 2001; 142(1):487-92. DOI: 10.1210/endo.142.1.7883. View

Chaillan C, Rogalska E, Chapus C, Lombardo D . A cross-linked complex between horse pancreatic lipase and colipase. FEBS Lett. 1989; 257(2):443-6. DOI: 10.1016/0014-5793(89)81592-3. View

Nagy T, Clair A . Precision and accuracy of dual-energy X-ray absorptiometry for determining in vivo body composition of mice. Obes Res. 2000; 8(5):392-8. DOI: 10.1038/oby.2000.47. View

10.

Locket P, Gallaher D . An improved procedure for bile acid extraction and purification and tissue distribution in the rat. Lipids. 1989; 24(3):221-3. DOI: 10.1007/BF02535238. View

11.

Bays H . Current and investigational antiobesity agents and obesity therapeutic treatment targets. Obes Res. 2004; 12(8):1197-211. DOI: 10.1038/oby.2004.151. View

12.

Smith S, Cases S, JENSEN D, Chen H, Sande E, Tow B . Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet. 2000; 25(1):87-90. DOI: 10.1038/75651. View

13.

Farmer J . Hypertension and the metabolic syndrome. Curr Cardiol Rep. 2004; 6(6):427-33. DOI: 10.1007/s11886-004-0050-7. View

14.

Chen H, Jensen D, Myers H, Eckel R, Farese Jr R . Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1. J Clin Invest. 2003; 111(11):1715-22. PMC: 156099. DOI: 10.1172/JCI15859. View

15.

Takahashi N, Lopez M, Cowhig Jr J, Taylor M, Hatada T, Riggs E . Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol. 2004; 16(1):125-32. DOI: 10.1681/ASN.2004060490. View

16.

Tsang S, Cheng C, Leung P . The role of the pancreatic renin-angiotensin system in acinar digestive enzyme secretion and in acute pancreatitis. Regul Pept. 2004; 119(3):213-9. DOI: 10.1016/j.regpep.2004.02.003. View

17.

Brodie B, Costa E, Dlabac A, Neff N, SMOOKLER H . Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J Pharmacol Exp Ther. 1966; 154(3):493-8. View

18.

Crandall D, Armellino D, Busler D, Kral J . Angiotensin II receptors in human preadipocytes: role in cell cycle regulation. Endocrinology. 1999; 140(1):154-8. DOI: 10.1210/endo.140.1.6430. View

19.

Bowers R, Festuccia W, Song C, Shi H, Migliorini R, Bartness T . Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol. 2004; 286(6):R1167-75. DOI: 10.1152/ajpregu.00558.2003. View

20.

Surwit R, Kuhn C, Cochrane C, McCubbin J, Feinglos M . Diet-induced type II diabetes in C57BL/6J mice. Diabetes. 1988; 37(9):1163-7. DOI: 10.2337/diab.37.9.1163. View