Soluble Receptor for Advanced Glycation End Products (sRAGE) Isoforms Predict Changes in Resting Energy Expenditure in Adults with Obesity during Weight Loss

Collin J Popp, Boyan Zhou, Michaele B Manigrasso, Huilin Li, Margaret Curran, Lu Hu, David E St-Jules, José O Alemán, Sally M Vanegas, Melanie Jay, Michael Bergman, Eran Segal, Mary A Sevick, Ann M Schmidt, Collin J Popp, Boyan Zhou, Michaele B Manigrasso, Huilin Li, Margaret Curran, Lu Hu, David E St-Jules, José O Alemán, Sally M Vanegas, Melanie Jay, Michael Bergman, Eran Segal, Mary A Sevick, Ann M Schmidt

Abstract

Background: Accruing evidence indicates that accumulation of advanced glycation end products (AGEs) and activation of the receptor for AGEs (RAGE) play a significant role in obesity and type 2 diabetes. The concentrations of circulating RAGE isoforms, such as soluble RAGE (sRAGE), cleaved RAGE (cRAGE), and endogenous secretory RAGE (esRAGE), collectively sRAGE isoforms, may be implicit in weight loss and energy compensation resulting from caloric restriction.

Objectives: We aimed to evaluate whether baseline concentrations of sRAGE isoforms predicted changes (∆) in body composition [fat mass (FM), fat-free mass (FFM)], resting energy expenditure (REE), and adaptive thermogenesis (AT) during weight loss.

Methods: Data were collected during a behavioral weight loss intervention in adults with obesity. At baseline and 3 mo, participants were assessed for body composition (bioelectrical impedance analysis) and REE (indirect calorimetry), and plasma was assayed for concentrations of sRAGE isoforms (sRAGE, esRAGE, cRAGE). AT was calculated using various mathematical models that included measured and predicted REE. A linear regression model that adjusted for age, sex, glycated hemoglobin (HbA1c), and randomization arm was used to test the associations between sRAGE isoforms and metabolic outcomes.

Results: Participants (n = 41; 70% female; mean ± SD age: 57 ± 11 y; BMI: 38.7 ± 3.4 kg/m2) experienced modest and variable weight loss over 3 mo. Although baseline sRAGE isoforms did not predict changes in ∆FM or ∆FFM, all baseline sRAGE isoforms were positively associated with ∆REE at 3 mo. Baseline esRAGE was positively associated with AT in some, but not all, AT models. The association between sRAGE isoforms and energy expenditure was independent of HbA1c, suggesting that the relation was unrelated to glycemia.

Conclusions: This study demonstrates a novel link between RAGE and energy expenditure in human participants undergoing weight loss.This trial was registered at clinicaltrials.gov as NCT03336411.

Keywords: caloric restriction; energy balance; metabolic adaptation; precision nutrition; resting metabolic rate.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Flow of participants through the 3-mo dietary intervention. The flow diagram includes the 2 arms (Standardized and Personalized) collapsed into a single group.

References

    1. Kelly T, Yang W, Chen C-S, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32(9):1431–7.
    1. Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE. A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. J Gerontol A Biol Sci Med Sci. 2015;70(9):1097–104.
    1. Fothergill E, Guo J, Howard L, Kerns JC, Knuth ND, Brychta R. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24(8):1612–19.
    1. Martins C, Roekenes J, Gower BA, Hunter GR. Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets. Nutr Metab (Lond). 2021;18(1):60.
    1. Gaens KHJ, Goossens GH, Niessen PM, van Greevenbroek MM, van der Kallen CJH, Niessen HW. Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance. Arterioscler Thromb Vasc Biol. 2014;34(6):1199–208.
    1. Semba RD, Arab L, Sun K, Nicklett EJ, Ferrucci L. Fat mass is inversely associated with serum carboxymethyl-lysine, an advanced glycation end product, in adults. J Nutr. 2011;141(9):1726–30.
    1. Gugliucci A, Kotani K, Taing J, Matsuoka Y, Sano Y, Yoshimura M. Short-term low calorie diet intervention reduces serum advanced glycation end products in healthy overweight or obese adults. Ann Nutr Metab. 2009;54(3):197–201.
    1. Uribarri J, del Castillo MD, de la Maza MP, Filip R, Gugliucci A, Luevano-Contreras C. Dietary advanced glycation end products and their role in health and disease. Adv Nutr. 2015;6(4):461–73.
    1. Deo P, Keogh JB, Price NJ, Clifton PM. Effects of weight loss on advanced glycation end products in subjects with and without diabetes: a preliminary report. Int J Environ Res Public Health. 2017;14(12):1553.
    1. Tavares JF, Ribeiro PVM, Coelho OGL, da Silva LE, Alfenas RCG. Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review. Obes Rev. 2020;21(6):e13000.
    1. Brix JM, Höllerl F, Kopp HP, Schernthaner GH, Schernthaner G. The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity. Int J Obes. 2012;36(11):1412–17.
    1. Lorenzi R, Pattou F, Beuscart JB, Grossin N, Lambert M, Fontaine P. Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is independent of previous diabetic status. Diabetes Metab. 2014;40(5):356–62.
    1. Horwitz D, Padron C, Kelly T, Saunders JK, Ude-Welcome A, Schmidt A-M. Long-term outcomes comparing metabolic surgery to no surgery in patients with type 2 diabetes and body mass index 30–35. Surg Obes Relat Dis. 2020;16(4):503–8.
    1. Hagen I, Schulte DM, Müller N, Martinsen J, Türk K, Hedderich J. Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects. Cytokine. 2015;73(2):265–9.
    1. Miranda ER, Fuller KNZ, Perkins RK, Kroeger CM, Trepanowski JF, Varady KA. Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health. Nutr Metab Cardiovasc Dis. 2018;28(11):1155–65.
    1. Song F, del Pozo CH, Rosario R, Zou YS, Ananthakrishnan R, Xu X. RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice. Diabetes. 2014;63(6):1948–65.
    1. Hurtado del Pozo C, Ruiz HH, Arivazhagan L, Aranda JF, Shim C, Daya P. A receptor of the immunoglobulin superfamily regulates adaptive thermogenesis. Cell Rep. 2019;28(3):773–91.e7.
    1. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163(5):1079–94.
    1. Popp CJ, St-Jules DE, Hu L, Ganguzza L, Illiano P, Curran M. The rationale and design of the personal diet study, a randomized clinical trial evaluating a personalized approach to weight loss in individuals with pre-diabetes and early-stage type 2 diabetes. Contemp Clin Trials. 2019;79:80–8.
    1. Weir J. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949;109(1–2):1–9.
    1. Popp CJ, Butler M, Curran M, Illiano P, Sevick MA, St-Jules DE. Evaluating steady-state resting energy expenditure using indirect calorimetry in adults with overweight and obesity. Clin Nutr. 2020;39(7):2220–6.
    1. Nunes CL, Jesus F, Francisco R, Matias CN, Heo M, Heymsfield SB. Adaptive thermogenesis after moderate weight loss: magnitude and methodological issues. Eur J Nutr. 2022;61(3):1405–16.
    1. Schmidt AM, Hori O, Brett J, Yan SD, Wautier JL, Stern D. Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb. 1994;14(10):1521–8.
    1. Dozio E, Briganti S, Delnevo A, Vianello E, Ermetici F, Secchi F. Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women. Eur J Nutr. 2017;56(8):2557–64.
    1. Miranda ER, Somal VS, Mey JT, Blackburn BK, Wang E, Farabi S. Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes. Am J Physiol Endocrinol Metab. 2017;313(6):E631–40.
    1. Norata GD, Garlaschelli K, Grigore L, Tibolla G, Raselli S, Redaelli L. Circulating soluble receptor for advanced glycation end products is inversely associated with body mass index and waist/hip ratio in the general population. Nutr Metab Cardiovasc Dis. 2009;19(2):129–34.
    1. Koyama H, Yamamoto H, Nishizawa Y. RAGE and soluble RAGE: potential therapeutic targets for cardiovascular diseases. Mol Med. 2007;13(11–12):625–35.
    1. Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E, Hall KD. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012;97(7):2489–96.
    1. Tremblay A, Royer MM, Chaput JP, Doucet É. Adaptive thermogenesis can make a difference in the ability of obese individuals to lose body weight. Int J Obes. 2013;37(6):759–64.
    1. Galgani JE, Santos JL. Insights about weight loss-induced metabolic adaptation. Obesity (Silver Spring). 2016;24(2):277–8.
    1. Johnstone AM, Murison SD, Duncan JS, Rance KA, Speakman JR. Factors influencing variation in basal metabolic rate include fat-free mass, fat mass, age, and circulating thyroxine but not sex, circulating leptin, or triiodothyronine. Am J Clin Nutr. 2005;82(5):941–8.
    1. Pontzer H, Yamada Y, Sagayama H, Ainslie PN, Andersen LF, Anderson LJ. Daily energy expenditure through the human life course. Science. 2021;373(6556):808–12.
    1. ten Haaf T, Verreijen AM, Memelink RG, Tieland M, Weijs PJM. Reduction in energy expenditure during weight loss is higher than predicted based on fat free mass and fat mass in older adults. Clin Nutr. 2018;37(1):250–3.
    1. Odetti P, Traverso N, Cosso L, Noberasco G, Pronzato MA, Marinari UM. Good glycaemic control reduces oxidation and glycation end-products in collagen of diabetic rats. Diabetologia. 1996;39(12):1440–7.
    1. Gelžinský J, Mayer O, Seidlerová J, Mateřánková M, Mareš Š, Kordíkova V. Serum biomarkers, skin autofluorescence and other methods. Which parameter better illustrates the relationship between advanced glycation end products and arterial stiffness in the general population?. Hypertens Res. 2021;44(5):518–27.
    1. Basman C, Fishman SL, Avtanski D, Rashid U, Kodra A, Chen K. Glycosylated hemoglobin, but not advanced glycation end products, predicts severity of coronary artery disease in patients with or without diabetes. Metabol Open. 2020;7:100050.
    1. Ying L, Shen Y, Zhang Y, Wang Y, Liu Y, Yin J. Association of advanced glycation end products with lower-extremity atherosclerotic disease in type 2 diabetes mellitus. Front Cardiovasc Med. 2021;8:696156.
    1. Rabbani N, Thornalley PJ. Glyoxalase 1 modulation in obesity and diabetes. Antioxid Redox Signaling. 2019;30(3):354–74.
    1. Müller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity (Silver Spring). 2013;21(2):218–28.
    1. Redman LM, Heilbronn LK, Martin CK, de Jonge L, Williamson DA, Delany JP. Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS One. 2009;4(2):e4377.
    1. Müller MJ, Wang Z, Heymsfield SB, Schautz B, Bosy-Westphal A. Advances in the understanding of specific metabolic rates of major organs and tissues in humans. Curr Opin Clin Nutr Metab Care. 2013;16(5):501–8.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit