The metabolic syndrome is a condition characterised by abnormal metabolic regulation that involves dysfunction to the blood glucose, blood lipid, energy regulatory and fat storage systems. The metabolic syndrome is characterised by insulin resistance, and this reduction in insulin sensitivity is likely the causative agent in the metabolic dysfunction. One of the main physiological changes associated with the development of the metabolic syndrome is a change to the lipid metabolism in the liver. In this regard the de novo lipogenesis pathway is activated and fatty acid production accelerated. This increases plasma levels of triglycerides, which are also referred to as very low density lipoproteins (VLDL), and increases the lipids stored in both hepatic and peripheral tissues. As VLDL is transformed into low density lipoprotein (LDL) in the circulation, the LDL fraction of plasma also increases. Increases in blood glucose levels also exacerbates the dysfunction seen to lipid metabolism in the metabolic syndrome.
Certain flavonoid may be beneficial at preventing or reversing the metabolic syndrome. In particular the flavonoid subclass flavanones may have beneficial effects against the dyslipidaemia that develops as part of the metabolic syndrome. Flavanones are found in high abundance in citrus fruit in their glycoside (joined to a sugar) form and these include naringin and hesperidin. Other flavonoids found in citrus fruit include flavones such as nobiletin and tangeretin, and these too may have beneficial effects against dyslipidaemia. Following consumption of citrus, naringin and hesperidin require hydrolysis to remove the sugar moiety before absorption can proceed while nobiletin and tangeretin are aglycones which do not have a sugar moiety. Following absorption these flavonoids are found in the circulation in a conjugated form, following extensive metabolism in the enterocytes of the gut and in the liver. Evidence suggest that citrus flavonoids are bioactive and have beneficial effects in humans.
Absorption of citrus flavonoids does not appear to lower energy intake or inhibit lipid absorption in animal experiments, and so the lipid lowering effects are likely not through changes to dietary energy intake of the animals. Therefore the beneficial effects are likely biochemical and occur at a tissue level. In the liver, citrus flavonoids may reduce flux through the de novo lipogenesis pathways and at the same time increase fatty acid oxidation. This would account for the ability of citrus flavonoids to reduce fatty liver disease in rodent models. The reduction in the production of triglycerides in the liver and the increased fatty acid oxidation also explains the triglyceride lowering effects of citrus flavonoids. The lower plasma triglyceride levels also explain to some extent the lower triglyceride content of peripheral tissue such as the skeletal muscle, following consumption of citrus flavonoids. Therefore part of the lipid lowering effects of the citrus flavonoids likely derive from direct lipid lowering effects.
However, citrus flavonoids may also favourable modify glucose metabolism. For example citrus flavonoids may increase glucose uptake by skeletal muscle and the liver through an insulin sensitising effect. Consumption of citrus flavonoids may therefore decrease blood glucose levels, which may in turn lower lipid synthesis rates in the liver. This may also explain the ability of citrus flavonoids to protect from diet induced accumulation of subcutaneous and visceral adipose tissue. Certain citrus flavonoids may also increase whole body energy expenditure, although the exact mechanism by which this occurs is not fully understood. This could lower both blood glucose and lipid concentrations. The ability of citrus flavonoids to reduce inflammation in adipose and hepatic tissue is consistent with the antioxidant effects of the flavonoid group of chemicals, and may explain the cardioprotective effects of citrus flavonoids. Citrus fruit consumption may therefore explain some of the observed protective effects of fruits against the development of metabolic syndrome.
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