Cooperative action of bioactive components in milk fat with PPARs may explain its anti-diabetogenic properties.

Type 2 diabetes and its comorbidity insulin resistance is a major public health problem in developed countries and those with the disorder have up to a fourfold increased risk of cardiovascular disease relative to those without the disease. The cardiovascular complications are believed to be due largely to multiple mechanisms relating to hyperglycemia that defines the disease. Overweight and obesity are the predominant risk factors and lifestyle changes aimed at reducing weight and increasing physical activity are the basis for prevention and treatment of type 2 diabetes. The role of diet in type 2 diabetes has been investigated widely, but the results have been inconclusive. Recently two large meta-analyses of prospective cohort studies found that dairy product consumption was inversely associated with the risk of type 2 diabetes. Numerous observational studies including large prospective studies found that a high intake of dairy fat or markers of dairy fat were inversely associated with the risk of type 2 diabetes. These observations suggest that dairy fat could contain components with anti-diabetogenic properties. Candidates for the antidiabetic affect are rumenic and vaccenic acids, phytanic and pristanic acids vitamin A and β-carotene and butyric acid. The role of these compounds in glucose homeostasis and energy balance is discussed. A common feature is that all are agonists for one or more of the three PPAR isoforms that are expressed in metabolically active tissue, such as the liver, skeletal muscle and adipose tissue where they play a critical role in regulating energy balance and the metabolism of fatty acids and glucose, the main energy sources. Because PPARs have a larger ligand binding pocket than other nuclear receptors they can be activated by a wide range of agonists. Whereas individual components may not be present in sufficient concentration to produce a physiological effect such an effect may be obtained by several components acting in concert, and forms the basis of the hypothesis. PPAR agonists such as anthocyanidins and resveratrol present in nondairy items may also contribute to outcome. In addition, PPAR-α, -β and -γ are abundant in brown adipose tissue where agonists and cold exposure induce uncoupling protein-1 expression in the mitochondria where it acts to generate heat at the expense of storing energy. Animal studies demonstrated that most milk fat bioactive compounds induced uncoupling protein-1 expression in brown adipose tissue, which was associated with suppression of diet-induced obesity and improvement in insulin sensitivity.