Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats

Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrom...

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Autores principales:	Sanja Kovačević, Jelena Brkljačić, Danijela Vojnović Milutinović, Ljupka Gligorovska, Biljana Bursać, Ivana Elaković, Ana Djordjevic
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	fructose diet inflammation visceral adipose tissue insulin resistance female rats Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/905fd938f884403ea653a8ba960c182f
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spelling	oai:doaj.org-article:905fd938f884403ea653a8ba960c182f2021-11-11T10:34:58ZFructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats2296-861X10.3389/fnut.2021.749328https://doaj.org/article/905fd938f884403ea653a8ba960c182f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnut.2021.749328/fullhttps://doaj.org/toc/2296-861XIntroduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.Sanja KovačevićJelena BrkljačićDanijela Vojnović MilutinovićLjupka GligorovskaBiljana BursaćIvana ElakovićAna DjordjevicFrontiers Media S.A.articlefructose dietinflammationvisceral adipose tissueinsulin resistancefemale ratsNutrition. Foods and food supplyTX341-641ENFrontiers in Nutrition, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fructose diet inflammation visceral adipose tissue insulin resistance female rats Nutrition. Foods and food supply TX341-641
spellingShingle	fructose diet inflammation visceral adipose tissue insulin resistance female rats Nutrition. Foods and food supply TX341-641 Sanja Kovačević Jelena Brkljačić Danijela Vojnović Milutinović Ljupka Gligorovska Biljana Bursać Ivana Elaković Ana Djordjevic Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
description	Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.
format	article
author	Sanja Kovačević Jelena Brkljačić Danijela Vojnović Milutinović Ljupka Gligorovska Biljana Bursać Ivana Elaković Ana Djordjevic
author_facet	Sanja Kovačević Jelena Brkljačić Danijela Vojnović Milutinović Ljupka Gligorovska Biljana Bursać Ivana Elaković Ana Djordjevic
author_sort	Sanja Kovačević
title	Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
title_short	Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
title_full	Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
title_fullStr	Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
title_full_unstemmed	Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
title_sort	fructose induces visceral adipose tissue inflammation and insulin resistance even without development of obesity in adult female but not in male rats
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/905fd938f884403ea653a8ba960c182f
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Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats

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