@article{
author = "Kovačević, Sanja and Brkljačić, Jelena and Vojnović-Milutinović, Danijela and Gligorovska, Ljupka and Bursać, Biljana and Elaković, Ivana and Đorđević, Ana",
year = "2021",
abstract = "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,
VATmass and histology, and systemic insulin sensitivity. VAT insulin signaling andmarkers
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 PPARg 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 NFkB,
increased expression of proinflammatory cytokines (IL-1b, 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.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Nutrition",
title = "Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats",
volume = "8",
doi = "10.3389/fnut.2021.749328",
pages = "749328"
}
