The effect of a low compared to a high glycemic index/saturated fatty acid diet on hepatic fat

The liver plays an important role in fat metabolism. Disturbances in liver fat
metabolism can lead to accumulation of fat in the liver. This hepatic fat
storage is also called non-alcoholic fatty liver, when excessive alcohol use is
not the cause. A non-alcoholic fatty liver is associated with negative effects
on metabolic health, such as cardiovascular disease and type II diabetes.

Nutrition can influence liver fat storage. However, not only the amount fats
and carbohydrates, but also their quality have been shown to influence liver
fat. The few studies performed show that diets high in saturated fatty acids
(SFA) and diets with a high glycemic index (GI) increase liver fat content.
However, the diets in these studies are unrealistic compared to current dietary
guidelines. Here we want to combine low GI/SFA on the one hand and high GI/SFA
on the other hand to reflect realistically a healthy and an unhealthy diet as
they are actually consumed by the Dutch population. We exptect that a low
GI/SFA diet results in lower liver fat content compared to a high GI/SFA diet.

Primary Objective:
To investigate whether a two-week low compared to high GI/SFA diet reduces
liver fat content.

Exploratory Objectives:
To investigate whether a two-week low compared to high GI/SFA diet:
* reduces DNL
* lowers the 24-hour glycemic response
* lowers hepatic glycogen content
* increases plasma BHB levels
* changes hepatic lipid composition
* changes other plasma metabolites related to energy expenditure
* changes energy expenditure and substrate oxidation

This is a randomized cross-over study comparing the effects of a 2-week high
GI/SFA compared to a 2-week low GI/SFA diet. The diets will be interspersed by
a washout period of minimal 4 weeks.

Participants will adhere to two diets differing in GI and SFA content for 2
weeks each: a two-week low GI/low SFA diet and a two-week high GI/high SFA
diet. Diets will be comparable in macronutrient content, but will differ in
fatty acid composition and GI. Examples of products included in the low GI/low
SFA diet include: semi-skimmed milk, rye bread, bulgur, brown rice, tuna,
chicken, turkey, nuts, fresh vegetables. Examples of products included in the
low GI/low SFA diet include: Potatoes, meatballs, beef, chocolate pudding,
white bread, mature 48+ cheese, orange juice.
Energy percentages (en%) of carbohydrates, fats and protein will be matched and
will be around 55-60, 25-30, 10-15, respectively. The intended fatty acid
composition of the low GI/SFA diet is 6, 10 and 12 en% saturated,
mono-unsaturated and poly-unsaturated respectively, while for the high GI/SFA
en% will be 14, 10 and 4, respectively. The intended GI of the low GI/SFA diet
will be 35-40% and the intended GI of the high GI/SFA diet 60-65%.

Results of this study will provide insight in the effect of a low GI/SFA
compared to a high GI/SFA diet on liver fat and will provide information on the
potential mechanisms underlying these effects on liver fat. The risks of the
performed measurements and the physical discomfort are low; risks related to
the MRS measurements and meal-test are low because of clear exclusion criteria
aimed at reducing risks and the well-experienced researchers performing these
tests and isotopically-labelled water ingestion is entirely safe and non-toxic
with body water enrichment up to 20 mol%.