Role of Heme Oxygenase in Inflammation, Insulin-signalling, Diabetes and Obesity

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2010 May 29

PMID 20508722

Citations 61

Authors

Joseph Fomusi Ndisang

Affiliations

Soon will be listed here.

Abstract

Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-alpha), interleukin (IL-6), IL-1beta and resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-kappaB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-kappaB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.

Citing Articles

Natural Chalcones for the Management of Obesity Disease.

Maisto M, Marzocchi A, Keivani N, Piccolo V, Summa V, Tenore G Int J Mol Sci. 2023; 24(21).

PMID: 37958912 PMC: 10648025. DOI: 10.3390/ijms242115929.

Proteomic analysis of the effect of hemin in breast cancer.

Colo G, Schweitzer K, Oresti G, Alonso E, Chavez L, Mascaro M Sci Rep. 2023; 13(1):10091.

PMID: 37344532 PMC: 10284804. DOI: 10.1038/s41598-023-35125-4.

The Na/K-ATPase: A potential therapeutic target in cardiometabolic diseases.

Obradovic M, Sudar-Milovanovic E, Gluvic Z, Banjac K, Rizzo M, Isenovic E Front Endocrinol (Lausanne). 2023; 14:1150171.

PMID: 36926029 PMC: 10011626. DOI: 10.3389/fendo.2023.1150171.

Fatty Liver/Adipose Tissue Dual-Targeting Nanoparticles with Heme Oxygenase-1 Inducer for Amelioration of Obesity, Obesity-Induced Type 2 Diabetes, and Steatohepatitis.

Hong J, Kim Y Adv Sci (Weinh). 2022; 9(33):e2203286.

PMID: 36209391 PMC: 9685446. DOI: 10.1002/advs.202203286.

Artemisia argyi extract alleviates inflammation in a DSS-induced colitis mouse model and enhances immunomodulatory effects in lymphoid tissues.

Shin J, Son Y, Ha I, Erdenebileg S, Jung D, Song D BMC Complement Med Ther. 2022; 22(1):64.

PMID: 35277165 PMC: 8917695. DOI: 10.1186/s12906-022-03536-x.

References

Lira V, Soltow Q, Long J, Betters J, Sellman J, Criswell D . Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle. Am J Physiol Endocrinol Metab. 2007; 293(4):E1062-8. DOI: 10.1152/ajpendo.00045.2007. View

Potenza M, Marasciulo F, Chieppa D, Brigiani G, Formoso G, Quon M . Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol. 2005; 289(2):H813-22. DOI: 10.1152/ajpheart.00092.2005. View

Ozcan U, Cao Q, Yilmaz E, Lee A, Iwakoshi N, Ozdelen E . Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004; 306(5695):457-61. DOI: 10.1126/science.1103160. View

Karalis K, Giannogonas P, Kodela E, Koutmani Y, Zoumakis M, Teli T . Mechanisms of obesity and related pathology: linking immune responses to metabolic stress. FEBS J. 2009; 276(20):5747-54. DOI: 10.1111/j.1742-4658.2009.07304.x. View

Tsai J, Zhang R, Qiu W, Su Q, Naples M, Adeli K . Inflammatory NF-kappaB activation promotes hepatic apolipoprotein B100 secretion: evidence for a link between hepatic inflammation and lipoprotein production. Am J Physiol Gastrointest Liver Physiol. 2009; 296(6):G1287-98. DOI: 10.1152/ajpgi.90540.2008. View

Hotamisligil G . Inflammation and metabolic disorders. Nature. 2006; 444(7121):860-7. DOI: 10.1038/nature05485. View

Mohri T, Ogura H, Koh T, Fujita K, Sumi Y, Yoshiya K . Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome. J Trauma. 2006; 61(3):616-23. DOI: 10.1097/01.ta.0000238228.67894.d7. View

Klover P, Zimmers T, Koniaris L, Mooney R . Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. 2003; 52(11):2784-9. DOI: 10.2337/diabetes.52.11.2784. View

Ndisang J, Moncini M, Gai P, Berni L, Cecere G, Masini E . Induction of heme oxygenase provides protection against cardiac anaphylaxis. Inflamm Res. 2000; 49 Suppl 1:S76-7. DOI: 10.1007/PL00000193. View

10.

Steinberg G, Watt M, Febbraio M . Cytokine Regulation of AMPK signalling. Front Biosci (Landmark Ed). 2009; 14(5):1902-16. DOI: 10.2741/3350. View

11.

Lima N, Abbasi F, Lamendola C, Reaven G . Prevalence of insulin resistance and related risk factors for cardiovascular disease in patients with essential hypertension. Am J Hypertens. 2008; 22(1):106-11. DOI: 10.1038/ajh.2008.263. View

12.

Cai D, Yuan M, Frantz D, Melendez P, Hansen L, Lee J . Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005; 11(2):183-90. PMC: 1440292. DOI: 10.1038/nm1166. View

13.

Jonas J, Guiot Y, Rahier J, Henquin J . Haeme-oxygenase 1 expression in rat pancreatic beta cells is stimulated by supraphysiological glucose concentrations and by cyclic AMP. Diabetologia. 2003; 46(9):1234-44. DOI: 10.1007/s00125-003-1174-9. View

14.

Shibahara S, Nakayama M, Kitamuro T, Udono-Fujimori R, Takahashi K . Repression of heme oxygenase-1 expression as a defense strategy in humans. Exp Biol Med (Maywood). 2003; 228(5):472-3. DOI: 10.1177/15353702-0322805-08. View

15.

Ma J, Lau C, Obed A, Dada A, Doenecke A, Fan S . A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury. Gene Ther. 2008; 16(3):320-8. DOI: 10.1038/gt.2008.162. View

16.

Fajas L, Debril M, Auwerx J . PPAR gamma: an essential role in metabolic control. Nutr Metab Cardiovasc Dis. 2001; 11(1):64-9. View

17.

Ndisang J, Jadhav A . Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes. Am J Physiol Endocrinol Metab. 2009; 296(4):E829-41. DOI: 10.1152/ajpendo.90783.2008. View

18.

Wild S, Roglic G, Green A, Sicree R, King H . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047-53. DOI: 10.2337/diacare.27.5.1047. View

19.

Bhatt B, Dube J, Dedousis N, Reider J, ODoherty R . Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type dependent manner. Am J Physiol Regul Integr Comp Physiol. 2005; 290(1):R233-40. DOI: 10.1152/ajpregu.00097.2005. View

20.

Feinstein R, Kanety H, Papa M, Lunenfeld B, Karasik A . Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem. 1993; 268(35):26055-8. View