Increased Plasma Lipopolysaccharide-binding Protein and Altered Inflammatory Mediators in Overweight Women Suggest a State of Subclinical Endotoxemia

Overview

Journal Res Sq

Date 2023 Oct 16

PMID 37841878

Authors

Christine N Metz

Xiangying Xue

Prodyot K Chatterjee

Robert P Adelson

Michael Brines

Kevin J Tracey

Peter K Gregersen

Valentin A Pavlov

Affiliations

Soon will be listed here.

Abstract

Chronic low-grade inflammation has been recognized as an underlying event linking obesity to cardiovascular disease (CVD). However, inflammatory alterations in individuals who are overweight remain understudied. To provide insight, we determined the levels of key circulating biomarkers of endotoxemia and inflammation, including lipopolysaccharide-binding protein (LBP), CRP, IL-6, leptin, and adiponectin in adult female subjects (n = 20) who were lean or overweight and had high cholesterol and/or high blood pressure - two important conventional risk factors for CVD. Plasma levels of LBP (a recognized marker of metabolic endotoxemia in obesity) were significantly higher in the overweight group compared with the lean group (P = 0.005). The levels of CRP, a general marker of inflammation, were also significantly higher in overweight subjects (P = 0.01), as were IL-6 (P = 0.02) and leptin (P = 0.002), pro-inflammatory mediators associated with cardiovascular risk. Levels of adiponectin, an adipokine with anti-inflammatory and anti-atherogenic functions, were significantly lower in the overweight group (P = 0.002). The leptin/adiponectin ratio, a preferential atherogenic marker was significantly increased in women who are overweight (P = 0.02). LBP, CRP, leptin, and adiponectin levels significantly correlated with BMI, but not with age. These results reveal the presence of subclinical endotoxemia and a pro-inflammatory state in overweight women and are of interest for further studies with the goal for improved understanding of women's cardiovascular health.

References

Mathieu P, Lemieux I, Despres J . Obesity, inflammation, and cardiovascular risk. Clin Pharmacol Ther. 2010; 87(4):407-16. DOI: 10.1038/clpt.2009.311. View

Esser N, Paquot N, Scheen A . Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert Opin Investig Drugs. 2014; 24(3):283-307. DOI: 10.1517/13543784.2015.974804. View

Rexrode K, Pradhan A, Manson J, Buring J, Ridker P . Relationship of total and abdominal adiposity with CRP and IL-6 in women. Ann Epidemiol. 2003; 13(10):674-82. DOI: 10.1016/s1047-2797(03)00053-x. View

Roberts L, Buford T . Lipopolysaccharide binding protein is associated with CVD risk in older adults. Aging Clin Exp Res. 2020; 33(6):1651-1658. PMC: 7937758. DOI: 10.1007/s40520-020-01684-z. View

de Gusmao Correia M, Haynes W . Leptin, obesity and cardiovascular disease. Curr Opin Nephrol Hypertens. 2004; 13(2):215-23. DOI: 10.1097/00041552-200403000-00010. View

Konstantinides S, Schafer K, Koschnick S, Loskutoff D . Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest. 2001; 108(10):1533-40. PMC: 209418. DOI: 10.1172/JCI13143. View

Albillos A, de la Hera A, Gonzalez M, Moya J, Calleja J, Monserrat J . Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology. 2002; 37(1):208-17. DOI: 10.1053/jhep.2003.50038. View

Saltiel A, Olefsky J . Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017; 127(1):1-4. PMC: 5199709. DOI: 10.1172/JCI92035. View

Cohen J . The detection and interpretation of endotoxaemia. Intensive Care Med. 2000; 26 Suppl 1:S51-6. DOI: 10.1007/s001340051119. View

10.

Nakamura K, Fuster J, Walsh K . Adipokines: a link between obesity and cardiovascular disease. J Cardiol. 2013; 63(4):250-9. PMC: 3989503. DOI: 10.1016/j.jjcc.2013.11.006. View

11.

Pischon T, Girman C, Hotamisligil G, Rifai N, Hu F, Rimm E . Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004; 291(14):1730-7. DOI: 10.1001/jama.291.14.1730. View

12.

Shetty G, Economides P, Horton E, Mantzoros C, Veves A . Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care. 2004; 27(10):2450-7. DOI: 10.2337/diacare.27.10.2450. View

13.

Elks C, Francis J . Central adiposity, systemic inflammation, and the metabolic syndrome. Curr Hypertens Rep. 2010; 12(2):99-104. DOI: 10.1007/s11906-010-0096-4. View

14.

Vors C, Pineau G, Drai J, Meugnier E, Pesenti S, Laville M . Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial. J Clin Endocrinol Metab. 2015; 100(9):3427-35. DOI: 10.1210/JC.2015-2518. View

15.

Schenck-Gustafsson K . Risk factors for cardiovascular disease in women. Maturitas. 2009; 63(3):186-90. DOI: 10.1016/j.maturitas.2009.02.014. View

16.

Gregor M, Hotamisligil G . Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011; 29:415-45. DOI: 10.1146/annurev-immunol-031210-101322. View

17.

Wilson P, DAgostino R, Sullivan L, Parise H, Kannel W . Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002; 162(16):1867-72. DOI: 10.1001/archinte.162.16.1867. View

18.

Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M . Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003; 107(5):671-4. DOI: 10.1161/01.cir.0000055188.83694.b3. View

19.

Ross R, Neeland I, Yamashita S, Shai I, Seidell J, Magni P . Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020; 16(3):177-189. PMC: 7027970. DOI: 10.1038/s41574-019-0310-7. View

20.

Kotani K, Sakane N, Saiga K, Kurozawa Y . Leptin : adiponectin ratio as an atherosclerotic index in patients with type 2 diabetes : relationship of the index to carotid intima-media thickness. Diabetologia. 2005; 48(12):2684-6. DOI: 10.1007/s00125-005-0015-4. View