Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol

Pektaş, Mehmet Bilgehan; Koca, Halit Buğra; Sadı, Gökhan; Akar, Fatma

doi:10.1155/2016/8014252

Cited by 60 publications

(63 citation statements)

References 42 publications

(56 reference statements)

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“…In agreement with other reports, we also found an increase in inflammatory markers (IL-6, IL-1β and TNFα) and a decrease in anti-inflammatory markers (CD206: M2 marker and IL-10 ) in EAT from FRD mice [31,[47][48][49][50]. Moreover, adipocytes isolated from FRD mice showed an inflammatory response (higher IL-6 release) that worsened when the obese phenotype was more evident (FRD 10 weeks).…”

Section: Accepted Manuscriptsupporting

confidence: 92%

M1 macrophage subtypes activation and adipocyte dysfunction worsen during prolonged consumption of a fructose-rich diet

Gambaro

Zubiría

Portales

et al. 2018

The Journal of Nutritional Biochemistry

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Fructose-rich diet (FRD) has been associated with obesity development, which is characterized by adipocytes hypertrophy and chronic low-grade inflammation. Interaction of adipocytes and immune cells plays a key role in adipose tissue (AT) alterations in obesity. We assessed the metabolic and immune impairments in AT in a murine obesity model induced by FRD at different periods. Adult Swiss mice were divided into groups of 6 and 10 weeks of fructose (FRD 6wk, FRD 10wk) or water intake (CTR 6wk, CTR 10wk). FRD induced increased in body weight, epidydimal AT mass, and plasmatic and liver Tg, and impaired insulin sensitivity. Also, hypertrophic adipocytes from FRD 6wk-10wk mice showed higher IL-6 when stimulated with LPS and leptin secretion. Several of these alterations worsened in FRD 10wk. Regarding AT inflammation, FRD mice have increased TNFα, IL-6 and IL1β, and decrease in IL-10 and CD206 mRNA levels. Using CD11b, LY6C, CD11c and CD206 as macrophages markers, we identified for first time in AT M1 (M1a: Ly6CCD11cCD206 and M1b: Ly6CCD11cCD206) and M2 subtypes (Ly6CCD11cCD206). M1a phenotype increased from 6 weeks onward, while Ly6C M1b phenotype increased only after 10 weeks. Finally, co-culture of RAW264.7 (monocytes cell line) and CTR or FRD adipocytes showed that FRD 10wk adipocytes increased IL-6 expression in non- or LPS-stimulated monocytes. Our results showed that AT dysfunction got worse as the period of fructose consumption was longer. Inflammatory macrophage subtypes increased depending on the period of FRD intake, and hypertrophic adipocytes were able to create an environment that favored M1 phenotype in vitro.

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Section: Accepted Manuscriptsupporting

confidence: 92%

M1 macrophage subtypes activation and adipocyte dysfunction worsen during prolonged consumption of a fructose-rich diet

Gambaro

Zubiría

Portales

et al. 2018

The Journal of Nutritional Biochemistry

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“…Under high fructose consumption, adipose tissue is the key site, giving rise to the secretion of inflammatory cytokines in systemic circulation [129]. Adipose dysfunction can disturb energy expenditure and insulin signaling mainly through inflammatory cytokines [130].…”

Section: Indirect Dangerous Factors In Tissue and Organ Dysfunctiomentioning

confidence: 99%

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

2017

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High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

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“…Namely, MIF can limit GCs effects, most likely through p38 phosphorylation, while the absence of endogenous MIF is associated with increased sensitivity to GCs through decreased phosphorylation of p38 MAPK (Calandra et al 1995, Aeberli et al 2006a. Proinflammatory p38 kinase is activated by oxidative stress and inflammation in 3T3-L1 cells and human adipocytes (Merkel et al 2002, Chuang et al 2010, Vazquez Prieto et al 2015, Cheng et al 2017, and fructose diet is known to enhance the production of proinflammatory cytokines and oxidative stress mediators in rodent visceral adipose tissue (Kovačević et al 2016, Pektas et al 2016. Our results showed that fructose diet indeed led to the elevation in both total and phospho p38 protein levels in WT and Mif-deficient mice.…”

Section: Figurementioning

confidence: 99%

Mif deficiency promotes adiposity in fructose-fed mice

Gligorovska

Bursać

Kovačević

et al. 2019

Journal of Endocrinology

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The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation, regulation of energy metabolism and glucocorticoid action. Chronic lowgrade inflammation may be caused by fructose intake, contributing to visceral adipose tissue (VAT) dysfunction. Since MIF is a known antagonist of glucocorticoid signaling, and deregulated glucocorticoid signaling can contribute to lipid metabolism disturbances, we hypothesized that altered MIF signaling might underlie fructose-induced adiposity through glucocorticoid action. We analyzed physiological and biochemical parameters, adipose tissue histology, insulin sensitivity and lipid metabolism in WT and MIF −/− C57Bl/6J mice consuming 20% fructose solution for 9 weeks. Glucocorticoid prereceptor metabolism and glucocorticoid receptor (GR) protein level were examined in VAT, together with the expression of glucocorticoid-target genes involved in lipid metabolism. The expression of adipogenic and lipogenic transcriptional regulators peroxisome proliferator-activated receptor gamma (PPARG) and sterol regulatory element-binding protein 1c (SREBP1c) was also assessed. Results showed disturbed insulin sensitivity in all MIF −/− mice, regardless of the diet. Mice on fructose diet had increased energy intake, but increased visceral adiposity and enlarged adipocytes were observed only in fructose-fed MIF −/− mice. Increased VAT corticosterone level and 11 beta-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase and GR protein levels were observed in the same animals, together with induced expression of examined lipogenic genes and accumulation of PPARG and SREBP1c. In conclusion, the results showed that dietary fructose was associated with increased visceral adiposity through activation of GR-regulated lipogenic genes, but only in the absence of MIF, which set the state of hyperinsulinemia and insulin resistance.

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Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol

Cited by 60 publications

References 42 publications

M1 macrophage subtypes activation and adipocyte dysfunction worsen during prolonged consumption of a fructose-rich diet

M1 macrophage subtypes activation and adipocyte dysfunction worsen during prolonged consumption of a fructose-rich diet

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

Mif deficiency promotes adiposity in fructose-fed mice

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