Influence of High-fat Overfeeding on Circulating Hepatokine Concentrations: a Randomised Crossover Study

In recent years, researchers have identified a number of liver-secreted proteins, termed "hepatokines", which are thought to play an important role in inter-organ crosstalk between the liver and other metabolically active tissues such as skeletal muscle and adipose tissue. Specifically, previous studies have demonstrated that hepatokines contribute to whole body glucose and lipid homeostasis through acting in an endocrine-like fashion. Understanding how circulating concentrations of these hepatokines can be manipulated in humans is essential, as impaired blood glucose and lipid control is a key feature of metabolic diseases, such as type 2 diabetes and non-alcoholic fatty liver disease.

Previous research at Loughborough University has found that acute high-fat overfeeding for up to seven days can impair glycaemic control; however, the exact mechanisms responsible for these detrimental changes are not fully understood. Based upon previous evidence that hepatokine production is nutritionally modulated, the investigators believe that changes in hepatokine production may play a role in the detrimental metabolic effects seen following short-term, high-fat overfeeding which has implications for long-term metabolic health.

Appetite regulation is also thought to play a role in the pathophysiology of obesity and insulin resistance, as the impaired secretion of several appetite regulatory hormones in both fasting and postprandial conditions has been observed in obesity, which is characterised by an chronic excessive energy intake. Therefore, the investigators are also interested to examine the appetite regulatory hormone response to short-term, high-fat overfeeding.

The present study is a randomised, controlled, crossover study in which twelve recreationally active, healthy males will consume both a hypercaloric, high-fat diet (consisting of 50% extra energy above the daily requirement, 65% of which is fat) and a control diet (the participants' habitual diet) in a randomised fashion. A three-week washout period will separate the two diets in order to remove any lasting effects confounding the subsequent diet.

Following a prescreening session in which anthropometric data will be collected, participants will commence their first dietary condition. An oral glucose tolerance test will be performed before and after the two diets to measure changes in glycaemic control/whole body insulin sensitivity. Further blood samples will be taken 24 hours and 72 hours after commencing the diets in order to observe the time course of any changes in circulating hepatokine and appetite hormone concentrations. Physical activity will also be monitored for the duration of the two dietary conditions to ensure that habitual physical activity levels are maintained.