Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences.

Very low-carbohydrate ketogenic diets (VLCKDs) are an emerging nutritional treatment for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD). Little is known about the effect of sex differences on weight loss induced by following a VLCKD. The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Forty-two females and 28 males with severe obesity underwent a 25-day VLCKD. Anthropometric parameters, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL) and a greater reduction in γ-glutamyl transferase (γGT) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL and γGT. No significant difference between groups was observed for improvement in the Edmonton stage or in the degree of steatosis. We conclude that the efficacy of following a VLCKD in severe obesity is affected by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences are attenuated after menopause, probably because of changes in hormonal profile and body composition.

Increased plasmatic NETs by-products in patients in severe obesity.

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.

Lysosomal Acid Lipase as a Molecular Target of the Very Low Carbohydrate Ketogenic Diet in Morbidly Obese Patients: The Potential Effects on Liver Steatosis and Cardiovascular Risk Factors.

A very low carbohydrate ketogenic diet (VLCKD) is an emerging technique to induce a significant, well-tolerated, and rapid loss of body weight in morbidly obese patients. The low activity of lysosomal acid lipase (LAL) could be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is a common feature in morbidly obese patients. Fifty-two obese patients suitable for a bariatric surgery intervention underwent a 25-day-long VLCKD. The biochemical markers of glucose and lipid metabolism, and flow-mediated dilation (FMD) of the brachial artery were measured before and after VLCKD. LAL activity was measured using the dried blood spot technique in 20 obese patients and in a control group of 20 healthy, normal-weight subjects. After VLCKD, we observed a significant reduction in body mass index, fasting glucose, insulinemia, and lipid profile parameters. No significant variation in FMD was observed. The number of patients with severe liver steatosis significantly decreased. LAL activity significantly increased, although the levels were not significantly different as compared to the control group. In conclusion, VLCKD induces the activity of LAL in morbidly obese subjects and reduces the secretion of all circulating lipoproteins. These effects could be attributed to the peculiar composition of the diet, which is particularly poor in carbohydrates and relatively rich in proteins.