(References included in () are located under ‘Key references’)
A negative correlation between milk intake and obesity (1;2) indicates that milk contains weight regulating component(s). This positive effect of dairy products on weight management in human intervention studies has recently focused on the lipid-binding effect of calcium in the intestine, but there is increasing evidence that the weight regulating effect of milk cannot be ascribed exclusively to calcium (3-6).
Recent experiments in our lab have shown that human epithelial cells exposed to milk up-regulate expression of the FIAF gene. FIAF, also known as PPARγ angio-poietin-related protein, angiopoietin-like protein 4 (Angptl4) or hepatic fibrinogen/-angiopoietin-related protein, has been shown to regulate lipid metabolism. Furthermore, in mice, we and others demonstrated that the absence of a gut flora (germfree mice) protected against diet-induced obesity, whereas this protection was reversed in germfree knockout mice lacking FIAF (7;8). In addition, over-expression of FIAF has proved to markedly reduce adipose tissue mass, partly due to stimulation of fatty acid oxidation and uncoupling in fat metabolism (9).
Although the exact role of FIAF is not clear, it inhibits lipoprotein lipase (LPL) (10), an enzyme that hydrolyzes the triglycerides in circulating lipoproteins to release fatty acids for uptake by adjacent tissues (11). Thus, FIAF may act in a paracrine manner to regulate the partitioning of fatty acids between sites of storage (adipose tissue) and sites of oxidation (heart, skeletal muscle, and liver).
In addition to lipid metabolism, FIAF has also been linked to decreased plasma glucose levels and improved glucose tolerance. Data are conflicting, and the role of FIAF in glucose homeostasis remains unclear (12). However, the majority of the studies published today have been performed in rodents, and the importance of FIAF in humans is relatively unknown.
The primary aim is to document the basic mechanisms and factors behind the observed beneficial effect of milk on body weight using animal and human intervention studies.
Effects of microorganisms on human metabolism may reflect the microbial diversity in the gut (10), which in turn may be affected by foods. Alternatively, the presence of a specific gut flora may modulate the effect of the FIAF-IMC. The human gut is populated by a complex ecosystem, the gut microbiota. Large individual variations in gut flora are observed in humans. Furthermore, different diets affect the gut microbiota, and thus, the assessment of the effect of FIAF-inducing activity will be coupled to analysis of the composition of the gut microbiota.
A secondary aim is therefore to investigate the impact of FIAF-milk inducing component(s) on the diversity of the gut flora and to examine the effect of a basic diet on the FIAF induction.
To fulfill the first and secondary aim, the project includes relevant animal models (mouse and pig) as well as human intervention studies, all of which supplement each other. The mouse models are far removed from the human species but enable mechanistic studies. By contrast, the pig model has greater resemblance to human physiology and enables more rigid experimental conditions and greater sampling availability compared to human studies (14). The ex vivo model on porcine intestinal explants has proven to be suitable for studies of dietary effects on intestinal function (15).
GC-MS and NMR are complementary techniques, which together provide a multi-metabolite analytical tool that may be used to explore the most dominant metabolites present in body fluids and obtain specific information on fatty acids and amino acid profiles of body fluids (16;17).
Finally, the impact of the cow breeding and milk processing steps on the presence, functionality, and stability of FIAF-milk inducing component(s) is examined to identify precautionary measures that the dairy industry should address to maintain FIAF-milk inducing component(s) activity.
Naturally, consumers need to be informed about the new findings in order to be able to benefit from them. New health benefits of basic foods may decrease the perceived naturalness of the product, especially if the benefit is based on a factor that consumers have not previously been aware of (13). The relevant research questions on consumer perception of health benefits are whether consumers find added value in new health benefits, how these benefits should be communicated, in what kind of dairy products they would be acceptable.
The tertiary aim is to investigate consumer perception and identify communication options with respect to milk and dairy products with FIAF-inducing properties.
Model and participants:
The five-year project will be organized in five scientific work packages, each directed by experts in the field. The integrated project activities are outlined in the figure below:
Figure 1: Work package overview and interactions. Dotted lines: information flow; thick arrows: sample flow.
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