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
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ Influx

Authors: Jian Chen, Li Li, Yingsha Li, Xia Liang, Qianqian Sun, Hao Yu, Jian Zhong, Yinxing Ni, Jing Chen, Zhigang Zhao, Peng Gao, Bin Wang, Daoyan Liu, Zhiming Zhu, Zhencheng Yan

Published in: Cardiovascular Diabetology | Issue 1/2015

Login to get access

Abstract

Background

The prevalence of obesity has dramatically increased worldwide and has attracted rising attention, but the mechanism is still unclear. Previous studies revealed that transient receptor potential vanilloid 1 (TRPV1) channels take part in weight loss by enhancing intracellular Ca2+ levels. However, the potential mechanism of the effect of dietary capsaicin on obesity is not completely understood. Ca2+ transfer induced by connexin43 (Cx43) molecules between coupled cells takes part in adipocyte differentiation. Whether TRPV1-evoked alterations in Cx43-mediated adipocyte-to-adipocyte communication play a role in obesity is unknown.

Materials and methods

We investigated whether Cx43 participated in TRPV1-mediated adipocyte lipolysis in cultured 3T3-L1 preadipocytes and visceral adipose tissues from humans and wild-type (WT) and TRPV1-deficient (TRPV1-/-) mice.

Results

TRPV1 and Cx43 co-expressed in mesenteric adipose tissue. TRPV1 activation by capsaicin increased the influx of Ca2+ in 3T3-L1 preadipocytes and promoted cell lipolysis, as shown by Oil-red O staining. These effects were deficient when capsazepine, a TRPV1 antagonist, and 18 alpha-glycyrrhetinic acid (18α-GA), a gap-junction inhibitor, were administered. Long-term chronic dietary capsaicin reduced the weights of perirenal, mesenteric and testicular adipose tissues in WT mice fed a high-fat diet. Capsaicin increased the expression levels of p-CaM, Cx43, CaMKII, PPARδ and HSL in mesenteric adipose tissues from WT mice fed a high-fat diet, db/db mice, as well as obese humans, but these effects of capsaicin were absent in TRPV1-/- mice. Long-term chronic dietary capsaicin decreased the body weights and serum lipids of WT mice, but not TRPV1-/- mice, fed a high-fat diet.

Conclusion

This study demonstrated that capsaicin activation of TRPV1-evoked increased Ca2+ influx in Cx43-mediated adipocyte-to-adipocyte communication promotes lipolysis in both vitro and vivo. TRPV1 activation by dietary capsaicin improves visceral fat remodeling through the up-regulation of Cx43.
Literature
1.
Gutierrez-Aguilar R, Kim DH, Woods SC, Seeley RJ. Expression of new loci associated with obesity in diet-induced obese rats: from genetics to physiology. Obesity (Silver Spring). 2012;20(2):306–12.CrossRef
2.
Després JP. Abdominal obesity and cardiovascular disease: is inflammation the missing link? Can J Cardiol. 2012;28(6):642–52.CrossRefPubMed
3.
de Souza RJ, Bray GA, Carey VJ, Hall KD, LeBoff MS, Loria CM, et al. Effects of 4 weight-loss diets differing in fat, protein, and carbohydrate on fat mass, lean mass, visceral adipose tissue, and hepatic fat: results from the POUNDS LOST trial. Am J Clin Nutr. 2012;95(3):614–25.CrossRefPubMedCentralPubMed
4.
5.
Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, 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
6.
Mathieu P, Pibarot P, Larose E, Poirier P, Marette A, Despres JP. Visceral obesity and the heart. Int J Biochem Cell Biol. 2008;40(5):821–36.CrossRefPubMed
7.
8.
Carmona Marinetto A, Lorenzo J. Intelligibility of language as a function of its consonant sounds. Study conducted in adult individuals with normal hearing. Acta Otorrinolaringol Esp. 1988;39(3):158–60.PubMed
9.
Lorenzo R. Diffuse interstitial pulmonary fibrosis in tobacco-industry workers. Arch Monaldi Mal Torace. 1988;43(3):235–41.PubMed
10.
Corsi M, Lorenzon G, Mesaglio S. Hepatic echography in acute viral hepatitis. Radiol Med. 1988;75(6):638–42.PubMed
11.
Yoshioka M, Lim K, Kikuzato S, Kiyonaga A, Tanaka H, Shindo M, et al. Effects of red-pepper diet on the energy metabolism in men. J Nutr Sci Vitaminol. 1995;41(6):647–56.CrossRefPubMed
12.
Yoshioka M, St-Pierre S, Suzuki M, Tremblay A. Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanese women. Br J Nutr. 1998;80(6):503–10.PubMed
13.
Marshall NJ, Liang L, Bodkin J, Dessapt-Baradez C, Nandi M, Collot-Teixeira S, et al. A role for TRPV1 in influencing the onset of cardiovascular disease in obesity. Hypertension. 2013;61(1):246–52.CrossRefPubMed
14.
Gram DX, Ahren B, Nagy I, Olsen UB, Brand CL, Sundler F, et al. Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. Eur J Neurosci. 2007;25(1):213–23.CrossRefPubMed
15.
Josse AR, Sherriffs SS, Holwerda AM, Andrews R, Staples AW, Phillips SM. Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise. Nutr Metab. 2010;7:65.CrossRef
16.
Lee TA, Li Z, Zerlin A, Heber D. Effects of dihydrocapsiate on adaptive and diet-induced thermogenesis with a high protein very low calorie diet: a randomized control trial. Nutr Metab. 2010;7:78.CrossRef
17.
Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr. 2003;90(3):651–9.CrossRefPubMed
18.
19.
Baboota RK, Singh DP, Sarma SM, Kaur J, Sandhir R, Boparai RK, et al. Capsaicin induces “brite” phenotype in differentiating 3T3-L1 preadipocytes. PLoS One. 2014;9(7):e103093.CrossRefPubMedCentralPubMed
20.
Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, et al. Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. Circ Res. 2007;100(7):1063–70.CrossRefPubMed
21.
Li Q, Li L, Wang F, Chen J, Zhao Y, Wang P, et al. Dietary capsaicin prevents nonalcoholic fatty liver disease through transient receptor potential vanilloid 1-mediated peroxisome proliferator-activated receptor delta activation. Pflugers Arch. 2013;465(9):1303–16.CrossRefPubMed
22.
Lorenzo M, Roncero C, Fabregat I, Benito M. Hormonal regulation of rat foetal lipogenesis in brown-adipocyte primary cultures. Biochem J. 1988;251(2):617–20.PubMedCentralPubMed
23.
Yanagiya T, Tanabe A, Hotta K. Gap-Junctional Communication Is Required for Mitotic Clonal Expansion during Adipogenesis. Obesity. 2007;15(3):572–82.CrossRefPubMed
24.
Yeganeh A, Stelmack GL, Fandrich RR, Halayko AJ, Kardami E, Zahradka P. Connexin 43 phosphorylation and degradation are required for adipogenesis. Biochim Biophys Acta. 2012;1823(10):1731–44.CrossRefPubMed
25.
Song D, Liu X, Liu R, Yang L, Zuo J, Liu W. Connexin 43 hemichannel regulates H9c2 cell proliferation by modulating intracellular ATP and [Ca2+]. Acta Biochim Biophys Sin (Shanghai). 2010;42(7):472–82.CrossRef
26.
Cappelluti G, Busilacchi P, Lorenzoni A. Surgical treatment of tumors of the extrahepatic bile ducts. Report on 5 years. Minerva Chir. 1988;43(11):929–33.PubMed
27.
Szatkowski C, Vallet J, Dormishian M, Messaddeq N, Valet P, Boulberdaa M, et al. Prokineticin Receptor 1 as a Novel Suppressor of Preadipocyte Proliferation and Differentiation to Control Obesity. PLoS One. 2013;8(12):e81175.CrossRefPubMedCentralPubMed
28.
Velasquez Almonacid L, Tafuri S, Dipineto L, Matteoli G, Fiorillo E, Morte RD, et al. Role of connexin-43 hemichannels in the pathogenesis of Yersinia enterocolitica. Vet J. 2009;182(3):452–7.CrossRefPubMed
29.
Kamioka H, Ishihara Y, Ris H, Murshid SA, Sugawara Y, Takano-Yamamoto T, et al. Primary cultures of chick osteocytes retain functional gap junctions between osteocytes and between osteocytes and osteoblasts. Microsc Microanal. 2007;13(2):108–17.CrossRefPubMed
30.
Gomes P, Srinivas SP, Vereecke J, Himpens B. Gap junctional intercellular communication in bovine corneal endothelial cells. Exp Eye Res. 2006;83(5):1225.CrossRefPubMed
31.
Shen J, Wang L, Zheng L, Zhu J, Hu S. Lovastatin inhibits gap junctional communication in cultured aortic smooth muscle cells. J Cardiovasc Pharmacol Ther. 2010;15(3):296–302.CrossRefPubMed
32.
Oviedo-Orta E, Howard Evans W. Gap junctions and connexin-mediated communication in the immune system. Biochim Biophys Acta. 2004;1662(1–2):102–12.CrossRefPubMed
33.
Sung B, Prasad S, Ravindran J, Yadav VR, Aggarwal BB. Capsazepine, a TRPV1 antagonist, sensitizes colorectal cancer cells to apoptosis by TRAIL through ROS-JNK-CHOP-mediated upregulation of death receptors. Free Radic Biol Med. 2012;53(10):1977–87.CrossRefPubMedCentralPubMed
34.
Haq N, Grose D, Ward E, Chiu O, Tigue N, Dowell SJ, et al. A high-throughput assay for connexin 43 (Cx43, GJA1) gap junctions using codon-optimized aequorin. Assay Drug Dev Technol. 2013;11(2):93–100.CrossRefPubMed
35.
Mohapatra DP, Nau C. Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. J Biol Chem. 2003;278(50):50080–90.CrossRefPubMed
36.
Ma W, Quirion R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin Ther Targets. 2007;11(3):307–20.CrossRefPubMed
37.
Marín J, Encabo A, Briones A, García-Cohen E-C, Alonso MJ. Mechanisms involved in the cellular calcium homeostasis in vascular smooth muscle: Calcium pumps. Life Sci. 1998;64(5):279–303.CrossRef
38.
Sun J, Pu Y, Wang P, Chen S, Zhao Y, Liu C, et al. TRPV1-mediated UCP2 upregulation ameliorates hyperglycemia-induced endothelial dysfunction. Cardiovasc Diabetol. 2013;12:69.CrossRefPubMedCentralPubMed
39.
Zemel MB. Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications. J Am Coll Nutr. 2002;21(2):146S–51.CrossRefPubMed
40.
Argilés JM, López-Soriano FJ, Busquets S. Therapeutic potential of interleukin-15: a myokine involved in muscle wasting and adiposity. Drug Discov Today. 2009;14(3):208–13.CrossRefPubMed
41.
Zhang SW, Liu Y, Huang GZ, Liu L. Aconitine alters connexin43 phosphorylation status and [Ca2+] oscillation patterns in cultured ventricular myocytes of neonatal rats. Toxicol In Vitro. 2007;21(8):1476–85.CrossRefPubMed
42.
Peracchia C, Sotkis A, Wang XG, Peracchia LL, Persechini A. Calmodulin directly gates gap junction channels. J Biol Chem. 2000;275(34):26220–4.CrossRefPubMed
43.
Xu Q, Kopp RF, Chen Y, Yang JJ, Roe MW, Veenstra RD. Gating of connexin 43 gap junctions by a cytoplasmic loop calmodulin binding domain. Am J Physiol Cell Physiol. 2012;302(10):C1548–56.CrossRefPubMedCentralPubMed
44.
Huang RY, Laing JG, Kanter EM, Berthoud VM, Bao M, Rohrs HW, et al. Identification of CaMKII phosphorylation sites in Connexin43 by high-resolution mass spectrometry. J Proteome Res. 2011;10(3):1098–109.CrossRefPubMedCentralPubMed
45.
Yamanouchi K, Yada E, Ishiguro N, Nishihara M. 18 alpha-glycyrrhetinic acid induces phenotypic changes of skeletal muscle cells to enter adipogenesis. Cell Physiol Biochem. 2007;20(6):781–90.CrossRefPubMed
46.
Schiller PC, D’Ippolito G, Brambilla R, Roos BA, Howard GA. Inhibition of gap-junctional communication induces the trans-differentiation of osteoblasts to an adipocytic phenotype in vitro. J Biol Chem. 2001;276(17):14133–8.PubMed
47.
Boitano S, Dirksen ER, Evans WH. Sequence-specific antibodies to connexins block intercellular calcium signaling through gap junctions. Cell Calcium. 1998;23(1):1–9.CrossRefPubMed
48.
Cotrina ML, Lin JH-C, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, et al. Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci U S A. 1998;95(26):15735–40.CrossRefPubMedCentralPubMed
49.
Nakagami T, Tanaka H, Dai P, Lin SF, Tanabe T, Mani H, et al. Generation of reentrant arrhythmias by dominant-negative inhibition of connexin43 in rat cultured myocyte monolayers. Cardiovasc Res. 2008;79(1):70–9.CrossRefPubMed
50.
Schalper KA, Sánchez HA, Lee SC, Altenberg GA, Nathanson MH, Sáez JC. Connexin 43 hemichannels mediate the Ca2+ influx induced by extracellular alkalinization. Am J Physiol Cell Physiol. 2010;299(6):C1504–15.CrossRefPubMedCentralPubMed
51.
Kurebayashi N, Nishizawa H, Nakazato Y, Kurihara H, Matsushita S, Daida H, et al. Aberrant cell-to-cell coupling in Ca2+-overloaded guinea pig ventricular muscles. Am J Physiol Cell Physiol. 2008;294(6):C1419–29.CrossRefPubMed
52.
Ahmed W, Ziouzenkova O, Brown J, Devchand P, Francis S, Kadakia M, et al. PPARs and their metabolic modulation: new mechanisms for transcriptional regulation? J Intern Med. 2007;262(2):184–98.CrossRefPubMed
53.
Tesauro B, Negro G, Percopo V, Lorenzo M. Thymectomy and myasthenia gravis. Critical remarks on our experience. Minerva Chir. 1988;43(17):1319–22.PubMed
54.
Desjardins JG, Bass J, Leboeuf G, Di Lorenzo M, Letarte J, Khan AH, et al. A twenty-year experience with thyroid carcinoma in children. J Pediatr Surg. 1988;23(8):709–13.CrossRefPubMed
55.
Di Lorenzo M, Collin PP. Pulmonary metastases in children: results of surgical treatment. J Pediatr Surg. 1988;23(8):762–5.CrossRefPubMed
56.
de Lorenzo V, Herrero M, Neilands JB. IS1-mediated mobility of the aerobactin system of pColV-K30 in Escherichia coli. Mol Gen Genet. 1988;213(2–3):487–90.CrossRefPubMed
57.
Jensen-Urstad AP, Semenkovich CF. Fatty acid synthase and liver triglyceride metabolism: Housekeeper or messenger? Biochim Biophys Acta. 2012;1821(5):747–53.CrossRefPubMedCentralPubMed
58.
He H, Yang D, Ma L, Luo Z, Ma S, Feng X, et al. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways. Hypertension. 2010;55(4):869–79.CrossRefPubMed
59.
Yang D, Luo Z, Ma S, Wong WT, Ma L, Zhong J, et al. Activation of TRPV1 by dietary capsaicin improves endothelium-dependent vasorelaxation and prevents hypertension. Cell Metab. 2010;12(2):130–41.CrossRefPubMedCentralPubMed
Metadata
Title
Activation of TRPV1 channel by dietary capsaicin improves visceral fat remodeling through connexin43-mediated Ca2+ Influx
Authors
Jian Chen
Li Li
Yingsha Li
Xia Liang
Qianqian Sun
Hao Yu
Jian Zhong
Yinxing Ni
Jing Chen
Zhigang Zhao
Peng Gao
Bin Wang
Daoyan Liu
Zhiming Zhu
Zhencheng Yan
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0183-6

Other articles of this Issue 1/2015

Cardiovascular Diabetology 1/2015 Go to the issue

Original investigation

Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet

Review

Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes

Original investigation

Vitamin D status is associated with skin autofluorescence in patients with type 2 diabetes mellitus: a preliminary report

Original investigation

Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow-up study

Original investigation

Chronic NF-κB blockade improves renal angiotensin II type 1 receptor functions and reduces blood pressure in Zucker diabetic rats

Original investigation

Type 2 diabetes-associated carotid plaque burden is increased in patients with retinopathy compared to those without retinopathy
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits