Examining the effects of short-term energy restriction on liver lipid, metabolism and inflammatory status in severely obese adults

A pre-operative energy restrictive diet is common practice prior to bariatric surgery in the United Kingdom. A review of current practice found variability in form, duration and application of the diet used, with little evidence for efficacy beyond patients successfully undergoing surgery. Imperative for best practice was to provide evidence of the efficacy of dietary approaches both in terms of the original aim of the diet to reduce liver size and improve access to enable laparoscopic surgery, but also to investigate the wider effects of the diet on this population. A clinical trial was designed to compare two very low energy dietary approaches applied over two weeks before bariatric surgery, using a) a food-based diet, which is standard practice at the Royal Derby Hospital, and comparing this to b) an alternative meal replacement approach with products supplied by LighterLife. The diets were designed to offer similar energy intakes, 800kcal/d, but with varying macronutrient composition and format. Both diets achieved comparable body weight loss (median -3.4%) and excess body mass index loss (median -1.79kg/m2). The trial found similar results from both diets for the original aim of the diet, which is to enable surgery. Surgeons’ visual assessment of the liver at the time of surgery for operative difficulty was associated to histologically assessed levels of steatosis, with lower levels of steatosis associated to less operative difficulty. Patient evaluation of the diets revealed no significant difference in outcomes between diets, and overall satisfaction of the diets was very high, with 92% and 85% reporting that they were satisfied or very satisfied with their diet respectively. Both diets produced a favourable change in circulating lipids, inflammatory markers and glucose (pooled median LDL -0.4mmol/L, Glucose-0.2mmol/L, CRP -3.6mg/L, IL6 -0.4pg/mL, ELF -0.8). Findings including histology and gene expression data suggest a dynamic lipid environment in both liver and omental adipose tissue post-diet, concurrent with insulin sensitivity, but suggest a less dynamic environment in subcutaneous adipose tissue. Overall the diets could not be separated in terms of effects on circulating biomarkers, Non-Alcoholic Fatty Liver disease outcomes, operative difficulty, gene expression levels, or patient acceptability. Negative associations with diabetes status were found for steatosis and inflammation post-diet and warrant further investigation. Also, childhood weight status was found to be linked to the level of improvement in insulin sensitivity and requires further work. Limitations suggest additional work should incorporate reporting or recording of physical activity levels, pre-diet assessment of liver condition, diabetes duration and habitual dietary intake. Work should also confirm findings and corroborate suppositions regarding physiological changes observed from mRNA transcript expression levels, into protein and onto functional levels. This work informs the format and application of a short-term pre-operative diet in severe obesity. It has established that pre-bariatric surgery patients were satisfied with either format of VLED when applied in clinical practice. It has also extended the existing evidence base on the effects of a short-term VLED, specifically the potential beneficial effects on progressive features of NAFLD, and adipose tissue inflammatory status, which could be of value in the management of the disease