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.

Stefano Ministrini,Maria Teresa Paganelli,Giulia Daviddi,Giulia Tozzi,Lucia Calzini,Graziana Lupattelli,Maria Anastasia Ricci,Elisa Nulli Migliola,Eva-Edvige Martorelli,Donatella Siepi,Anna Rita Roscini

doi:10.3390/jcm8050621

Abstract

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.

Highlights

Fatty liver disease is a very common feature of obesity [1] and it significantly contributes to the surgical risk involved in bariatric interventions, since it increases the risk of intra-operatory mechanical liver damage [2].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 [3]
Previous studies demonstrated an amelioration of glucose metabolism and endothelial function, measured as flow-mediated dilation (FMD), in obese patients after VLCKD; the results are still conflicting about the effects on FMD [4,5,6,7,8,9,10]
We evaluated if a relationship exists between the effects of VLCKD on lysosomal acid lipase (LAL) activity and other anthropometric, cardiovascular, and metabolic modifications induced by VLCKD in morbidly obese subjects

Summary

Introduction

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 [3]. VLCKD has been recently used to bring about immediate preoperative weight loss in patients suitable for bariatric surgery interventions. It simplifies anesthesiologic and surgical maneuvers in these patients and it reduces the risk of pre- and post-operative complications. Since the amount of weight loss obtained with VLCKD is related to the improvement in liver volume and steatosis [12], it has been hypothesized that the efficacy of pre-operative VLCKD is, at least in part, attributable to its effect on liver steatosis [13]

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