Effect of dietary protein on lipid and glucose metabolism: implications for metabolic health

<strong>Abstract</strong> <strong>Background</strong>: Diet is an important factor in the development of the Metabolic Syndrome (Mets) and type 2 Diabetes Mellitus. Accumulation of intra hepatic lipid (IHL) can result in non-alcoholic fatty liver disease (NAFLD), which is sometimes considered the hepatic manifestation of Mets. Manipulation of the dietary macronutrient composition – altering either fat or simple carbohydrates – has the potential to change lipid storage in the liver. Protein also has this ability, however human data is scarce. Moreover, high dietary protein intake is linked with an increased type 2 Diabetes risk. Therefore, it is essential to study the metabolic consequences of changes in macronutrient composition focussing on altering dietary protein quantity. <strong>Objective</strong>: In this thesis the effects of dietary protein on metabolic health focusing on lipid and glucose metabolism were investigated in both observational studies as well as in a human dietary intervention trial. <strong>Methods</strong>: In an observational study (n=1283), Fatty Liver Index (FLI) was calculated and related to macronutrient consumption from dietary assessment data. In a controlled dietary intervention, participants (n=27) were assigned to either a control-diet for 4 weeks, or a high-fat, hypercaloric diet, with either a high-protein or a normal-protein content for two weeks, and vice versa. Measurements of IHL (1H-MRS) and blood plasma glucose and lipid concentrations were performed, both in the fasting state and following a meal. <strong>Results</strong>: In the observational study, the prevalence of fatty liver as indicated by an FLI>60, was 22.0%. Compared to persons with a normal FLI score of <30, protein intake was positively related with high FLI score >60 (OR: 1.26 per 1 en%, 95%CI 1.16-1.37). This was in particular the case for protein intake from animal sources. In the dietary intervention study, the high-protein diet compared to the normal-protein diet resulted in lower IHL and plasma TG concentrations (IHL: 0.35 ± 0.04 % vs. 0.51 ± 0.08 %; p=0.08; TG: 0.65 ± 0.03 vs. 0.77 ± 0.05 mmol/L; p=0.07). Furthermore, after the meal challenge the free fatty acids (FFA) response was significant different between all three intervention diets (p=0.03). Moreover, the postprandial glucose response was significantly lower after adaptation to NP compared with HP (p=0.03), without differences in the postprandial insulin responses (p=0.37). <strong>Conclusions</strong>: From data of the intervention study and observational studies reported in this thesis, it can be concluded that dietary protein intake is associated with alterations in metabolic profile, with both favourable and potential unfavorable health outcomes. On the short term increasing dietary protein in healthy subjects improved lipid metabolism, as seen by lower TG and IHL levels, but not glucose metabolism. On the long term, however, a high-protein intake was related to a fatty liver, and associated to insulin resistance.