Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2016

Open Access 01-12-2016 | Research article

Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study

Authors: Chengfu Cai, Mingzhu Lin, Yanfang Xu, Xuejun Li, Shuyu Yang, Huijie Zhang

Published in: BMC Medicine | Issue 1/2016

Login to get access

Abstract

Background

Neuregulin 4 (Nrg4) is a secreted adipokine recently identified as playing an important role in modulating systemic energy metabolism and the development of obesity-associated disorders. However, information is not available regarding the association between circulating Nrg4 and risk of metabolic syndrome (MetS) in humans.

Methods

We measured serum Nrg4 in 1212 obese adult subjects (aged 40 years or older), with a waist circumference greater than 90 cm for men or 80 cm for women, recruited from the community.

Results

MetS subjects had lower levels of circulating Nrg4 than healthy controls (P < 0.01). The prevalence of MetS was higher in subjects with lower levels of circulating Nrg4 compared to those with higher values (67.3 % vs. 57.4 %, P < 0.05). Likewise, subjects with low levels of circulating Nrg4 had high prevalence of raised fasting glucose and blood pressure, but there was no association with raised triglycerides and reduced HDL-c. In multivariable logistic regression analyses, increased serum Nrg4 was significantly associated with reduced risk of MetS (OR: 0.603; 95 % CI, 0.439–0.828; P = 0.002), adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic blood pressure, fasting glucose, triglyceride, HDL-c, HOMA-IR, and body fat mass; however, such associations with serum Nrg4 were not noted for each component of MetS.

Conclusions

These findings indicate that circulating Nrg4 concentrations are inversely associated with risk of MetS in obese Chinese adults, suggesting that circulating Nrg4 concentrations may be a protective factor in the development of MetS.
Appendix
Available only for authorised users
Literature
1.
Malik S, Wong ND, Franklin SS, Kamath TV, L’Italien GJ, Pio JR, Williams GR. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110(10):1245–50.CrossRefPubMed
2.
Liu L, Miura K, Fujiyoshi A, Kadota A, Miyagawa N, Nakamura Y, Ohkubo T, Okayama A, Okamura T, Ueshima H. Impact of metabolic syndrome on the risk of cardiovascular disease mortality in the United States and in Japan. Am J Cardiol. 2014;113(1):84–9.CrossRefPubMed
3.
Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985–3023.CrossRefPubMed
4.
Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA. 2015;313(19):1973–4.CrossRefPubMed
5.
Andrus B, Lacaille D. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. J Am Coll Cardiol. 2014;63(25 Pt A):2886.CrossRefPubMed
6.
Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH. The metabolic syndrome. Endocr Rev. 2008;29(7):777–822.CrossRefPubMed
7.
Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005;111(11):1448–54.CrossRefPubMed
8.
Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96(9):939–49.CrossRefPubMed
9.
Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, Rader DJ. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation. 2005;111(7):932–9.CrossRefPubMed
10.
Sook Lee E, Park SS, Kim E, Sook Yoon Y, Ahn HY, Park CY, Ho Yun Y, Woo Oh S. Association between adiponectin levels and coronary heart disease and mortality: a systematic review and meta-analysis. Int J Epidemiol. 2013;42(4):1029–39.CrossRefPubMed
11.
12.
Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, et al. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20(12):1436–43.CrossRefPubMedPubMedCentral
13.
Dai YN, Zhu JZ, Fang ZY, Zhao DJ, Wan XY, Zhu HT, Yu CH, Li YM. A case-control study: association between serum neuregulin 4 level and non-alcoholic fatty liver disease. Metabolism. 2015;64(12):1667–73.CrossRefPubMed
14.
Pan LL, Zhang HJ, Huang ZF, Sun Q, Chen Z, Li ZB, Yang SY, Li XY, Li XJ. Intrahepatic triglyceride content is independently associated with chronic kidney disease in obese adults: a cross-sectional study. Metabolism. 2015;64(9):1077–85.CrossRefPubMed
15.
Zhou BF, Cooperative Meta-Analysis Group of the Working Group on Obesity in China. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002;15(1):83–96.PubMed
16.
Zhang HJ, Zhang XF, Ma ZM, Pan LL, Chen Z, Han HW, Han CK, Zhuang XJ, Lu Y, Li XJ, et al. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J Hepatol. 2013;59(3):557–62.CrossRefPubMed
17.
Frimel TN, Deivanayagam S, Bashir A, O’Connor R, Klein S. Assessment of intrahepatic triglyceride content using magnetic resonance spectroscopy. J Cardiometab Syndr. 2007;2(2):136–8.CrossRefPubMed
18.
Japur CC, Penaforte FR, Chiarello PG, Monteiro JP, Vieira MN, Basile-Filho A. Harris-Benedict equation for critically ill patients: are there differences with indirect calorimetry? J Crit Care. 2009;24(4):628. e1-5.CrossRefPubMed
19.
Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet. 2005;366(9491):1059–62.CrossRefPubMed
20.
Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, et al. Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab. 2014;306(8):E945–64.CrossRefPubMedPubMedCentral
21.
Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest. 2013;123(8):3404–8.CrossRefPubMedPubMedCentral
22.
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.CrossRefPubMed
23.
Kozak LP, Harper ME. Mitochondrial uncoupling proteins in energy expenditure. Annu Rev Nutr. 2000;20:339–63.CrossRefPubMed
24.
Bakker LE, Boon MR, van der Linden RA, Arias-Bouda LP, van Klinken JB, Smit F, Verberne HJ, Jukema JW, Tamsma JT, Havekes LM, et al. Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: a prospective, case-controlled observational study. Lancet Diabetes Endocrinol. 2014;2(3):210–7.CrossRefPubMed
25.
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17.CrossRefPubMedPubMedCentral
26.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500–8.CrossRefPubMed
27.
Chondronikola M, Volpi E, Borsheim E, Porter C, Saraf MK, Annamalai P, Yfanti C, Chao T, Wong D, Shinoda K, et al. Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans. Cell Metab. 2016;23(6):1200–6.CrossRefPubMed
28.
Hoeke G, Kooijman S, Boon MR, Rensen PC, Berbee JF. Role of brown fat in lipoprotein metabolism and atherosclerosis. Circ Res. 2016;118(1):173–82.CrossRefPubMed
29.
Ma Y, Gao M, Liu D. Preventing high fat diet-induced obesity and improving insulin sensitivity through neuregulin 4 gene transfer. Sci Rep. 2016;6:26242.CrossRefPubMedPubMedCentral
30.
Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39–48.CrossRefPubMed
31.
Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–41.CrossRefPubMed
32.
Pfeifer A. NRG4: an endocrine link between brown adipose tissue and liver. Cell Metab. 2015;21(1):13–4.CrossRefPubMed
33.
Kang YE, Kim JM, Choung S, Joung KH, Lee JH, Kim HJ, Ku BJ. Comparison of serum Neuregulin 4 (Nrg4) levels in adults with newly diagnosed type 2 diabetes mellitus and controls without diabetes. Diabetes Res Clin Pract. 2016;117:1–3.CrossRefPubMed
34.
Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28(1):27–38.CrossRefPubMed
35.
Bernard JK, McCann SP, Bhardwaj V, Washington MK, Frey MR. Neuregulin-4 is a survival factor for colon epithelial cells both in culture and in vivo. J Biol Chem. 2012;287(47):39850–8.CrossRefPubMedPubMedCentral
Metadata
Title
Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study
Authors
Chengfu Cai
Mingzhu Lin
Yanfang Xu
Xuejun Li
Shuyu Yang
Huijie Zhang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2016
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-016-0703-6

Other articles of this Issue 1/2016

BMC Medicine 1/2016 Go to the issue

Research article

Improving comfort in people with dementia and pneumonia: a cluster randomized trial

Research article

Investigating the pertussis resurgence in England and Wales, and options for future control

Research article

Current state of ethics literature synthesis: a systematic review of reviews

Research article

Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial

Forum

Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate

Commentary

Benefits of the Mediterranean diet beyond the Mediterranean Sea and beyond food patterns