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. 2011 Feb;7(1):8-20.
doi: 10.5114/aoms.2011.20598. Epub 2011 Mar 8.

Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?

Affiliations

Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?

Stephanie Seneff et al. Arch Med Sci. 2011 Feb.

Abstract

The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.

Keywords: cholesterol; fructose; metabolic syndrome.

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Figures

Figure 1
Figure 1
Block diagram of proposed sequence of events leading to MetS. (1) Serum LDL (L) becomes glycated due to exposure to glucose and fructose. (2) Adipocytes depend upon apoE (E) to scavenge glycated LDL-C and transport it into HDL-A1 (H). (3) ApoE becomes damaged and adipocytes accumulate lipid droplets (F) and excess cholesterol (C) in their endoplasmic reticulum (ER). Meanwhile, plasma membrane becomes cholesterol-depleted. Stressed adipocytes release angiotensin-II (AT-II) which leads to sodium-hoarding and hypertension. (4) Macrophages enter adipose tissue to engulf cell debris from accumulating dead adipocytes, forming multi-nucleated giant cells. (5) Due to insufficient HDL-C, fatty deposits accumulate ectopically to buffer cholesterol supplies to the major organs
Figure 2
Figure 2
Endocytosis of normal LDL. This schematic represents the normal binding of the apolipoprotein (A) and absorption of an LDL particle (L), which has attached to the receptor (R). The activated receptor has caused the formation of a caveolus for absorption from the blood vessel (V) by endocytosis through the cell membrane (M). These functional membrane changes are facilitated by cholesterol and caveolin enrichments to the lipid raft area (C)
Figure 3
Figure 3
Failed Endocytosis of glycated LDL. In this schematic the lysine in apoB or E (A) has become damaged by glycation (D). Consequently, the receptor (R) is unable to recognize the LDL particle (L). The cell endocytosis via the cell membrane (M) does not occur. The damaged LDL will circulate until a less discriminating scavenger receptor in an adipose cell takes it up for recycling

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