HIF-1α protein rather than mRNA as a marker of hypoxia in adipose tissue in obesity: focus on “Inflammation is associated with a decrease of lipogenic factors in omental fat in women,” by Poulain-Godefroy et al.

Abstract

ENDOCRINE PHYSIOLOGY AND METABOLISMHIF-1α protein rather than mRNA as a marker of hypoxia in adipose tissue in obesity: focus on “Inflammation is associated with a decrease of lipogenic factors in omental fat in women,” by Poulain-Godefroy et al.Paul Trayhurn, Bohan Wang, and I. Stuart WoodPaul Trayhurn, Bohan Wang, and I. Stuart WoodPublished Online:01 Oct 2008https://doi.org/10.1152/ajpregu.90633.2008MoreSectionsPDF (34 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat we were interested to see the article by Poulain-Godefroy et al. (4) in which a global decrease in lipogenic markers was associated with the enhancement of inflammation in human adipose tissue, a relationship accentuated in diabetic subjects. The authors further show that expression levels of the inflammatory markers CD14 and IL-18 are increased in omental compared with subcutaneous adipose tissue, the depot differences being particularly evident for IL-18. This suggests that subcutaneous fat is less susceptible to inflammation than the visceral tissue, consistent with the link between visceral fat and the diseases associated with obesity.Poulain-Godefroy et al. (4) also examined the hypothesis that hypoxia may occur in clusters of adipocytes distant from the vasculature in adipose tissue in obesity, thus underpinning the inflammatory response that develops as fat mass expands (6, 7). However, no increase in the level of the mRNA encoding the α-subunit of the key hypoxia-inducible transcription factor HIF-1 was found in adipose tissue of lean and obese subjects; nor were there depot differences in HIF-1α mRNA level (4). At first glance, this appears incompatible with the “hypoxia hypothesis” (6, 7), although a previous study observed increased HIF-1α mRNA levels in adipose tissue of obese subjects, which fell with weight loss (1), and there is now direct evidence of hypoxia in adipose tissue of genetic and dietary-induced obese animals together with an increase in HIF-1α protein (3, 5, 10).A key question is whether HIF-1α mRNA is a good indicator of hypoxia in adipose tissue. While changes in mRNA level are normally paralleled by subsequent alterations in the amount of the encoded protein, this does not seem to be the case for HIF-1α in human adipocytes (6). Indeed, our studies on human fat cells in culture have shown that hypoxia (1% O2 or chemically-induced) leads to a marked increase (up to 8-fold) in HIF-1α protein, while HIF-1α mRNA level falls (by up to 4-fold) (8, 9). There are parallels in other systems, for example, THP-1 human monocytes where the HIF-1α mRNA level fell in undifferentiated cells (and was unchanged in differentiated cells) in response to hypoxia while HIF-1α protein increased (2). The explanation for this is not clear, but stabilization of HIF-1α protein may feed back to transcriptional regulation of the HIF-1α gene.There is emerging evidence in support of the hypoxia hypothesis in obese animals (3, 5, 10) and from studies on adipocytes in culture, as recently reviewed (6). We suggest that it is important to measure the amount of HIF-1α protein, rather than the mRNA level, as a key marker in studies examining whether hypoxia occurs in adipose tissue in human obesity.REFERENCES1 Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clément K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54: 2277–2286, 2005.Crossref | PubMed | ISI | Google Scholar2 Frede S, Stockmann C, Freitag P, Fandrey J. Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB. Biochem J 396: 517–527, 2006.Crossref | PubMed | ISI | Google Scholar3 Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56: 901–911, 2007.Crossref | PubMed | ISI | Google Scholar4 Poulain-Godefroy O, Lecoeur C, Pattou F, Frühbeck G, Froguel P. Inflammation is associated with a decrease of lipogenic factors in omental fat in women. Am J Physiol Regul Integr Comp Physiol 295: R1–R7, 2008.Link | ISI | Google Scholar5 Rausch ME, Weisberg SP, Vardhana P, Tortorielllo DV. Obesity in C57BL/6J mice is characterised by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obesity 32: 451–463, 2008.Crossref | PubMed | ISI | Google Scholar6 Trayhurn P, Wang B, Wood IS. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br J Nutr 100: 227–235, 2008.Crossref | PubMed | ISI | Google Scholar7 Trayhurn P, Wood IS. Adipokines: Inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92: 347–355, 2004.Crossref | PubMed | ISI | Google Scholar8 Wang B, Wood IS, Trayhurn P. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflügers Archiv Eur J Physiol 455: 479–492, 2007.Crossref | PubMed | ISI | Google Scholar9 Wang B, Wood IS, Trayhurn P. PCR arrays identify metallothionein-3 as a highly hypoxia-inducible gene in human adipocytes. Biochem Biophys Res Commun 368: 88–93, 2008.Crossref | PubMed | ISI | Google Scholar10 Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 293: E1118–E1128, 2007.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: P. Trayhurn, Obesity Biology Research Unit, School of Clinical Sciences, Univ. of Liverpool, Duncan Bldg., Liverpool L69 3GA, U.K. (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Collections Cited ByIron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity14 January 2022 | Scientific Reports, Vol. 12, No. 1Oxygenation of adipose tissue: A human perspective2 June 2019 | Acta Physiologica, Vol. 228, No. 1Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota12 February 2018 | The ISME Journal, Vol. 12, No. 7Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2Science Translational Medicine, Vol. 10, No. 432The consumption of n-3 polyunsaturated fatty acids differentially modulates gene expression of peroxisome proliferator-activated receptor alpha and gamma and hypoxia-inducible factor 1 alpha in subcutaneous adipose tissue of obese adolescents2 April 2013 | Endocrine, Vol. 45, No. 1Persistent organic pollutants meet adipose tissue hypoxia: does cross-talk contribute to inflammation during obesity?2 September 2013 | Obesity Reviews, Vol. 15, No. 1Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective studySurgery for Obesity and Related Diseases, Vol. 9, No. 4Hypoxia and Adipose Tissue Function and Dysfunction in ObesityPaul Trayhurn1 January 2013 | Physiological Reviews, Vol. 93, No. 1The inflammation highway: metabolism accelerates inflammatory traffic in obesity14 August 2012 | Immunological Reviews, Vol. 249, No. 1The macrophage at the intersection of immunity and metabolism in obesity28 October 2011 | Diabetology & Metabolic Syndrome, Vol. 3, No. 1Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue26 January 2010 | International Journal of Obesity, Vol. 34, No. 4Response to the letter to the editor: “HIF-1α protein rather than mRNA as a marker of hypoxia in adipose tissue in obesity,” by Trayhurn et al.Odile Poulain-Godefroy, and Philippe Froguel1 October 2008 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 295, No. 4 More from this issue > Volume 295Issue 4October 2008Pages R1097-R1097 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.90633.2008PubMed18832093History Published online 1 October 2008 Published in print 1 October 2008 Metrics