Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents

The type and the amount of dietary fat have a significant influence on the metabolic pathways involved in the development of obesity, metabolic syndrome, diabetes type 2 and cardiovascular diseases. However, it is unknown to what extent this modulation is achieved through DNA methylation. We assessed the effects of cholesterol intake, the proportion of energy intake derived from fat, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA), the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of MUFA+PUFA to SFA on genome-wide DNA methylation patterns in normal-weight and obese children. We determined the genome-wide methylation profile in the blood of 69 Greek preadolescents (∼10 years old) as well as their dietary intake for two consecutive weekdays and one weekend day. The methylation levels of one CpG island shore and four sites were significantly correlated with total fat intake. The methylation levels of 2 islands, 11 island shores and 16 sites were significantly correlated with PUFA/SFA; of 9 islands, 26 island shores and 158 sites with MUFA/SFA; and of 10 islands, 40 island shores and 130 sites with (MUFA+PUFA)/SFA. We found significant gene enrichment in 34 pathways for PUFA/SFA, including the leptin pathway, and a significant enrichment in 5 pathways for (MUFA+PUFA)/SFA. Our results suggest that specific changes in DNA methylation may have an important role in the mechanisms involved in the physiological responses to different types of dietary fat

Cephalic phase of insulin secretion and food stimulation in humans: a new perspective

Insulinemia and glycemia were measured at a 1-min interval at the hour of a lunch meal in human subjects. When no food was presented to naive subjects (n = 4), cyclic oscillations of insulinemia were found (period, 12-20 min; amplitude, 2.8-10.3 microU/ml). It is proposed that these spontaneous oscillations must be taken into consideration when evaluating the insulin response on cephalic contact with food stimuli; they might otherwise constitute a source of artifacts. Four subjects were then submitted to a series of four test meals scheduled at a 1-wk interval. Although their prandial glycemia remained comparable with preprandial values for the first 16 min of the meals, insulinemia often exhibited early peaks (within a few min after meal onset) whose amplitude appeared related to palatability conditions. Evidence suggests that the insulin peaks triggered by cephalic stimulation are Pavlovian reflexes that become conditioned to the test situation. A typical neuroendocrine response to alimentary frustration is also described. The results are discussed in perspective with animal works, in terms of the effects of neuroendocrine events on feeding behavior. </jats:p

Lipid droplet dynamics and insulin sensitivity upon a 5-day high-fat diet in Caucasians and South Asians

A 5-day High-Fat High-Calorie diet (HFHC-diet) reduces insulin-stimulated glucose disposal (Rd) in South Asian, but not Caucasian healthy lean males. We aimed to investigate if differences in myocellular lipid handling are underlying this differential response. A two-step hyperinsulinemic-euglycemic clamp and muscle biopsies were performed in 12 healthy lean Caucasian and South Asian males (BMI <25 kg/m(2), 19-25 years) before and after a 5-day HFHC-diet (regular diet + 375 mL cream/day; 1275 kcal/day; 94% fat). Triglyceride extractions and Western Blots for lipid droplet and mitochondrial proteins were performed. Intramyocellular lipid content and HFHC-diet response were similar between ethnicities (group effect: P = 0.094; diet effect: +similar to 30%, P = 0.044). PLIN5 protein content increased upon the HFHC-diet (P = 0.031) and tended to be higher in South Asians (0.87 +/- 0.42 AU vs. 1.35 +/- 0.58 AU, P = 0.07). 4-HNE tended to increase in South Asians upon the HFHC-diet (interaction effect: P = 0.057). In Caucasians Delta PLIN5 content correlated with Delta R-d (Caucasians: r = 0.756, P = 0.011; South Asians: r = -0.085, P = 0.816), while in South Asians Delta 4-HNE associated with Delta PLIN5 content (Caucasians: r = 0.312, P = 0.380; South Asians: r = 0.771, P = 0.003). These data indicate that in Caucasians, PLIN5 may be protective against HFHC-diet induced insulin resistance, which for reasons not yet understood is not observed in South Asians, who possess increased lipid peroxidation levels