Humans, like many other animals, are congenitally attracted to sweet tasting food. In nature, sweet food is rather scarce, yet it plays a valuable role in the struggle for survival. Sweet food (sugars) has several precious characteristics such as high metabolic power (ATP produced/time), metabolic versatility, and it is preferred by vital tissues, such as brain. Moreover, like fat, sweet food is a good source of energy (energy dense). For this reason, sweet food taste and intake are positively rewarded by the human brain. This positive reward response must hav e evolved to ensure the required energy intake via efficient food selection. However, with the introduction of mass production of refined carbohydrate (CHO) and sugar this ancestral reward system is revealing to be potentially deleterious for our health. There is a great deal of evidence showing that high refined CHO and sugar consumption is associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM).
In this thesis we elucidate some aspects of the impact of exposure to high or low refined CHO/sugar intake on human physiology. In chapter 2 , we present 2 studies. The first shows that overweight/obese (Ov/Ob) individuals perceive sweet (sucrose) solutions to be less sweet than lean (L) controls. However, the liking for sweet does not seem to differ between Ov/Ob and L individuals. Importantly, we have shown for the first time that implicit attitude towards sweet food/drinks is stronger among Ov/Ob than L people. The second study proves that 4 weeks of soft drink supplementation (2.1±0.2 g CHO per kg of body w eight a day) can alter taste perception of sweet in lean, lightly active subjects. Moreover, explicit preference for sweet was increased in a subgroup of participants with initial low preference for sweet. In chapter 3 , we also present 2 studies. In the first study, we hav e adopted an in vitro approach to investigate the role of high glucose availability on metabolism, glucose sensing, and insulin signalling in primary human myotubes established from needle muscle biopsies. We exposed the human myotubes to high D-glucose medium (15 mmol/ L) and high insulin (10 μg/ml) and this led to an increased g lycolytic activity and de novo lipogenesis, whereas oxidative capacity did not change. The expression of the glucose sensing protein MondoA was augmented by high glucose availability and so was the expression of thioredoxin-interacting protein (TXNIP), a protein linked to insulin resistance. Furthermore, exposure to a hyperglycemic condition diminished serine-threonine kinase Akt phosphorylation (thr 308) in response to insulin stimulation (100 nmol/L), revealing that high glucose availability can reduce insulin signalling response. In the second study we have analysed the effects of 4 weeks soft drink supplementation in lean, lightly active participants on metabolism and insulin sensitivity at whole body as well as cellular levels (muscle biopsies). This in vivo study shows various adverse health outcomes (i . e. increases in fat mass, and fasting glucose and insulin levels, and reduced basal fat oxidation) as a consequence of the soft drink consumption. Moreover, from the skeletal muscle analysis we found a strong trend towards an increase in MondoA protein expression and a decrease in glycogen synthase kinase -3 ~ phosphorylation 1 h after glucose load. The disturbed insulin signalling that we found in vitro, due to exposure to high glucose, was confirmed in vivo with the syrup based soft drink intervention.
In chapter 4 , we have adopted a two week low CHO and low energy regime in combination with a high intensity interval training (HIIT) to reduce exogenous and endogenous glucose availability with the aim to reduce the risk of T2DM in sedentary, obese individuals. The low CHO and low energy regime improved oral glucose insulin sensitivity, fat oxidation, and lipid profile in only two weeks. The addition of an energy-balanced HIIT was not sufficient to further enhance these parameters. However, HIIT improved cardiovascular fitness and preserved lean mass and circulating resistin levels.
In chapter 5, a case study of a diabetic patient is reported. The patient underwent 4 weeks of restricted CHO diet in combination with HIIT. This life style intervention has proven to be sufficient to reverse this patient's diabetic status. A randomized trial is required to verify these outstanding results.
In conclusion, the work presented in this thesis adds a large amount of original knowledge about the effects of refined CHO and sugar availability on a variety of physiological and also some psychological parameters. A stronger implicit drive to the consumption of sweet food/drinks was found in Ov/Ob individuals. One month of soft drink consumption is enough to change taste perception of sweet and increase preference for sweet in initial sweet dislikers. High sugar (glucose) availability and consequently high energy intake have deleterious effects on glucose regulation and metabolism at a whole body and a cellular level. Energy deficit and moderate CHO restriction (low exogenous glucose) seem to be effective in improving glucose regulation thereby reducing the risk of T2DM in obese individuals. HIIT (low endogenous glucose) per se does not further reduce the risk of T2DM, but does reduce the risk of cardiovascular diseases in obese, otherwise sedentary persons.