The
metabolic syndrome is a cluster of common pathologies:
abdominal obesity linked to an excess of visceral fat,
insulin resistance,
dyslipidemia and
hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in
fructose intake, which appears to be an important causative factor in the
metabolic syndrome. There is also experimental and clinical evidence that the amount of
magnesium in the western diet is insufficient to meet individual needs and that
magnesium deficiency may contribute to
insulin resistance. In recent years, several studies have been published that implicate subclinical chronic
inflammation as an important pathogenic factor in the development of
metabolic syndrome. Pro-inflammatory molecules produced by adipose tissue have been implicated in the development of
insulin resistance. The present review will discuss experimental evidence showing that the
metabolic syndrome, high
fructose intake and low
magnesium diet may all be linked to the inflammatory response. In many ways,
fructose-fed rats display the changes observed in the
metabolic syndrome and recent studies indicate that high-
fructose feeding is associated with
NADPH oxidase and
renin-
angiotensin activation. The production of
reactive oxygen species results in the initiation and development of
insulin resistance,
hyperlipemia and
high blood pressure in this model. In this rat model, a few days of experimental
magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory
cytokines, appearance of the
acute phase proteins and excessive production of
free radicals. Because
magnesium acts as a natural
calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular
calcium concentration. Potential mechanisms include the priming of phagocytic cells, the opening of
calcium channels, activation of
N-methyl-D-aspartate (
NMDA) receptors, the activation of
nuclear factor-kappaB (NFkB) and activation of the renin-angiotensin system. Since
magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing
insulin resistance when
magnesium deficiency is combined with a high-
fructose diet. Accordingly,
magnesium deficiency combined with a high-
fructose diet induces
insulin resistance,
hypertension,
dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of
inflammation and oxidative stress.