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Review
. 2019 Jun 7;20(11):2787.
doi: 10.3390/ijms20112787.

High Fructose Intake and Adipogenesis

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Free PMC article
Review

High Fructose Intake and Adipogenesis

Adrián Hernández-Díazcouder et al. Int J Mol Sci. .
Free PMC article

Abstract

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fructose intake promotes white adipose tissue accumulation through activating adipogenesis. In vitro experiments have also demonstrated that fructose alone induces adipogenesis by several mechanisms, including (1) triglycerides and very-low-density lipoprotein (VLDL) production by fructose metabolism, (2) the stimulation of glucocorticoid activation by increasing 11β-HSD1 activity, and (3) the promotion of reactive oxygen species (ROS) production through uric acid, NOX and XOR expression, mTORC1 signaling and Ang II induction. Moreover, it has been observed that fructose induces adipogenesis through increased ACE2 expression, which promotes high Ang-(1-7) levels, and through the inhibition of the thermogenic program by regulating Sirt1 and UCP1. Finally, microRNAs may also be involved in regulating adipogenesis in high fructose intake conditions. In this paper, we propose further directions for research in fructose participation in adipogenesis.

Keywords: ROS; adipogenesis; adipose tissue; angiotensin II; fructose; glucocorticoids; microRNAs; uric acid.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chronic fructose intake induces white adipose tissue (WAT) expansion. Chronic fructose intake increases fructose concentration in the peripheral venous blood, which may reach WAT. Fructose may promote adipogenesis through direct mechanisms such as uric acid and leptin resistance or indirect mechanisms such as glucocorticoids action, oxidative stress, the renin–angiotensin system (RAS) and the induction of microRNAs. WAT: White adipose tissue; GCs: Glucocorticoids; RAS: Renin–angiotensin system. Created with Biorender.com.
Figure 2
Figure 2
Fructose induces adipogenesis through very-low-density lipoprotein (VLDL) production and glucocorticoid (GC) signalling. (A) High fructose intake increases triglycerides and VLDL production, which induce adipogenesis by increasing PPARγ and aP2 expression. (B) Fructose metabolism in adipocytes promotes glucocorticoid activation by inducting 11β-HSD1. The effects of GCs in adipocyte precursors cells induce the expression of adipogenic genes through a few mechanisms. VLDL: Very-low-density lipoprotein; GCs: Glucocorticoids; GR: Glucocorticoid receptor; NADPH: Nicotinamide adenosine dinucleotide phosphate; 11β-HSD1: 11-beta hydroxysteroid dehydrogenase type 1; CREB: cAMP response element-binding protein; cAMP: Cyclic adenosine monophosphate; PDE3BB: Cyclic-nucleotide phosphodiesterase 3B; HPI: Hexose-phosphate isomerase; H6PD: Hexose-6-phosphate dehydrogenase. Created with Biorender.com.
Figure 3
Figure 3
Fructose-induced reactive oxygen species (ROS) production promotes adipogenesis. Fructose metabolism induces adipogenesis through increasing ROS production. ROS may be induced by uric acid, NADPH oxidase activity, mTORC1 signaling and AT1 receptor signaling. ROS: Reactive oxygen species; NADPH: Nicotinamide adenosine dinucleotide phosphate; XOR: Xanthine oxidase; FAS: Fatty acid synthase; C/EBPα: CCAAT-enhancer-binding protein α; PPARϒ: Peroxisome proliferator-activated receptor ϒ. Created with Biorender.com.
Figure 4
Figure 4
Fructose-induced adipogenesis through Ang-(1–7) and inhibition of thermogenesis. (A) Fructose metabolism promotes the conversion from Ang-II to Ang-(1–7) by increasing ACE2 activity. Mas receptor signaling induces the expression of adipogenic genes. (B) Sirt1 regulates the thermogenic program by inhibiting PPARγ and activating Wnt/β-catenin signalling. High fructose intake inhibits the thermogenic program by downregulating Sirt1 and UCP1 in WAT. ACE2: Angiotensin-converting enzyme 2; FAS: Fatty acid synthase; PPARϒ: Peroxisome proliferator-activated receptor ϒ; ACC: Acetyl-CoA carboxylase; aP2: Adipocyte protein 2; Sirt1: Sirtuin 1; UCP1: Uncoupling protein 1; Wnt: Wingless e Int. Created with Biorender.com.

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