Excessive fat in the liver is associated with impairments in metabolic health. Reducing the amount of carbohydrates and fat both have been shown to reduce liver fat. However, not only the amount fats and carbohydrates, but also their quality have been shown to influence liver fat. Diets high in saturated fatty acids (SFA) and diets with a high glycemic index (GI) have been shown to increase liver fat content. However, available data from human dietary intervention studies is limited and these studies did not reflect a realistic diet. In the present study a combination of low GI/SFA on the one hand and high GI/SFA on the other hand is used to reflect realistically a healthy and an unhealthy diet as they are actually consumed by the Dutch population.

The primary objective of this study is to investigate whether a two-week low compared to high GI/SFA diet reduces liver fat content. In addition, it will be investigated whether a two- week low compared to high GI/SFA diet reduces DNL, lowers the 24-hour glycemic response, lowers hepatic glycogen content, increases hepatic fat oxidation and changes hepatic lipid composition. Furthermore, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon the low and high GI/SFA diets.

Rationale:

Excessive fat in the liver is associated with impairments in metabolic health. Reducing the amount of carbohydrates and fat both have been shown to reduce liver fat. However, not only the amount fats and carbohydrates, but also their quality have been shown to influence liver fat. Diets high in saturated fatty acids (SFA) and diets with a high glycemic index (GI) have been shown to increase liver fat content. However, available data from human dietary intervention studies is limited and these studies did not reflect a realistic diet. Here the investigators 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. It is hypothesized that such a low compared to a high GI/SFA diet reduces liver fat content and possibly liver fat composition. Furthermore, underlying pathways involved in mediating those changes in liver fat are largely unknown. Hepatic lipid storage can originate from several metabolic pathways, including de novo lipogenesis (DNL) or decreased hepatic fat oxidation. Based on current literature the investigators hypothesize that with the diets chosen here, both DNL (by differences in GI) and fat oxidation (by differences in fat composition) will be involved in causing changes in liver fat.

Objective:

The primary objective of this study is to investigate whether a two-week low compared to high GI/SFA diet reduces liver fat content. In addition, it will be investigated whether a two- week low compared to high GI/SFA diet reduces DNL, lowers the 24-hour glycemic response, lowers hepatic glycogen content, increases hepatic fat oxidation and changes hepatic lipid composition. Furthermore, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon the low and high GI/SFA diets.

Study design:

This is a randomized cross-over study comparing the effects of a high GI/SFA compared to a low GI/SFA diet.

Study population:

Up to seventeen healthy overweight/obese males and postmenopausal females, aged between 45-75 years and BMI between 27-38 kg/m2 will participate in the study (minimally 13 volunteers need to finish the study).

Inclusion Criteria:

• Caucasian
• Male or postmenopausal female
• Aged 45-75 years at start of the study
• Body mass index (BMI) 27 - 38 kg/m2
• Stable dietary habits (no weight loss or gain >3kg in the past 3 months) Sedentary lifestyle (not more than 2 hours of sports per week)
• TG between 1.0 and 4.0 mmol/L

Exclusion Criteria:

• Type 2 diabetes
• Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's or dependent physician's opinion interfere with the study
• Contra-indication for MRI (which can be found in appendix II)
• Alcohol consumption of >2 servings per day
• Smoking
• Use of medication known to interfere with the safety of study procedures