Assessment of Protein Intake in the First Three Months after Sleeve Gastrectomy in Patients with Severe Obesity.

An adequate protein intake prevents the loss of fat-free mass during weight loss. Laparoscopic sleeve gastrectomy (SG) jeopardizes protein intake due to post-operative dietary restriction and intolerance to protein-rich foods. The purpose of this study is to evaluate protein intake in the first three months after SG. We evaluated, 1 month and 3 months after surgery, 47 consecutive patients treated with SG. Protein intake, both from foods and from protein supplementation, was assessed through a weekly dietary record. Patients consumed 30.0 ± 10.2 g of protein/day on average from foods in the first month, with a significant increase to 34.9 ± 4.8 g of protein/day in the third month (p = 0.003). The use of protein supplementation significantly increased total protein intake to 42.3 ± 15.9 g protein/day (p < 0.001) in the first month and to 39.6 ± 14.2 g of protein/day (p = 0.002) in the third one. Compliance with supplement consumption was 63.8% in the first month and only 21.3% in the third month. In conclusion, both one and three months after SG, protein intake from foods was not sufficient. The use of modular supplements seems to have a significant impact on protein intake, but nevertheless it remains lower than recommended.

White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

Diet approach before and after bariatric surgery.

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

Correction to: Diet approach before and after bariatric surgery.

The original version of this article unfortunately, has the incorrect title reported in the published paper.

Predicting Responses to Bariatric and Metabolic Surgery.

PURPOSE OF REVIEW: Bariatric surgery is today the most effective therapy for weight loss and reduction of comorbidity burden in patients with severe obesity. However, bariatric surgery does not benefit equally all the patients. A consistent variability in outcomes has been observed. Predicting responses to bariatric surgery could be an important tool in clinical practice, by improving patients' selection or by identifying patients in which more aggressive follow-up and post-operative intervention should be applied. Predictive factors for weight loss, weight regain, diabetes remission and recurrence are briefly reviewed in this paper. RECENT FINDINGS: Many pre-operative factors have been proposed as negative or positive predictors of body weight reduction after surgery. However, none of these factors has been consistently demonstrated to have a sufficiently strong predictive power to influence eligibility to bariatric surgery itself. Weight regain can occur after bariatric surgery and its probability seems to be more influenced by post-operative behavioral factors than by pre-operative predictors. Several effective scores have been developed to predict diabetes remission after surgery, however long-term maintenance and diabetes recurrence after surgery seem again more influenced by post-operative behaviors and weight loss maintenance. In general, more attention and active interventions to pre-operative and post-operative eating behaviors and lifestyle modifications are probably more important at the clinical level than the search of pre-operative predictors of long-term outcomes.

Psychological predictors of poor weight loss following LSG: relevance of general psychopathology and impulsivity.

PURPOSE: After bariatric surgery (BS) a significant minority of patients do not reach successful weight loss or tend to regain weight. In recent years, interest for the psychological factors that predict post-surgical weight loss has increased with the objective of developing interventions aimed to ameliorate post-surgical outcomes. In the present study, predictive models of successful or poor weight loss 12 months after BS were investigated considering pre-surgery level of psychopathological symptoms, dysfunctional eating behaviors and trait impulsivity at baseline (pre-surgery). METHODS: Sixty-nine patients with morbid obesity canditates for laparoscopic sleeve gastrectomy were assessed regarding metabolic and psychological dimensions. Successful post-surgery weight loss was defined as losing at least 50% of excess body weight (%EWL). RESULTS: Logistic models adjusted for patient sex, age and presence of metabolic diseases showed that the baseline presence of intense psychopathological symptoms and low attentional impulsivity predict poor %EWL (< 50%), as assessed 12-month post-surgery. CONCLUSIONS: The present findings suggest that intensity of general psychopathology and impulsivity, among other psychological factors, might affect post-surgery %EWL. Conducting adequate psychological assessment at baseline of patients candidates for BS seems to be crucial to orient specific therapeutic interventions. LEVEL OF EVIDENCE: Level III, case-control analytic study.

SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. OBJECTIVE: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. METHOD: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. RESULTS: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. CONCLUSIONS: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.

Modifications of Resting Energy Expenditure After Sleeve Gastrectomy.

OBJECTIVES: Resting energy expenditure (REE) declines more than what is expected according to body composition changes after caloric restriction. This metabolic adaptation is considered one of the factors favoring weight regain. The aim of this study is to evaluate the changes of REE and calculate the degree of metabolic adaptation occurring after laparoscopic sleeve gastrectomy (LSG). METHODS: REE (by indirect calorimetry) and body composition (fat-free mass or FFM, fat mass or FM by bioelectrical impedance analysis) were determined before and after 12 months in 154 patients with obesity treated with laparoscopic sleeve gastrectomy (LSG). RESULTS: Weight loss was 29.8 ± 10.6%, with corresponding relative reductions in FM (44.5 ± 22.8%), FFM (13.7 ± 9.9%), and REE (27.3 ± 12.9%). A predictive equation for REE was computed by using the baseline FFM and FM values to account for body composition changes. A predicted post-weight loss REE was calculated by using this equation and entering post-weight loss body composition values. Observed post-surgery REE was significantly lower than predicted one (1410 ± 312 vs 1611 ± 340 kcal/day, P < 0.001) and metabolic adaptation, calculated as the difference between observed and predicted post-weight loss REE, was - 199 ± 238 kcal/day. The post-surgery level of metabolic adaptation was inversely related to postoperative percent weight loss (r = - 0.170; P < 0.05) and FM loss (r = - 0.245; P < 0.01). CONCLUSIONS: A significant reduction of resting energy expenditure and a significant degree of metabolic adaptation both occur after sleeve gastrectomy. A greater metabolic adaptation could be partly responsible for a lower weight loss after surgery.

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity.

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.

Increased mitochondrial calcium uniporter in adipocytes underlies mitochondrial alterations associated with insulin resistance.

Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating the molecular identity and the physiological roles of the mitochondrial calcium uniporter (MCU) complex, we now have the tools to understand the functions of mitochondrial Ca2+ in the regulation of pathophysiological processes. Herein, we describe the role of key MCU complex components in insulin resistance in mouse and human adipose tissue. Adipose tissue gene expression was analyzed from several models of obese and diabetic rodents and in 72 patients with obesity as well as in vitro insulin-resistant adipocytes. Genetic manipulation of MCU activity in 3T3-L1 adipocytes allowed the investigation of the role of mitochondrial calcium uptake. In insulin-resistant adipocytes, mitochondrial calcium uptake increased and several MCU components were upregulated. Similar results were observed in mouse and human visceral adipose tissue (VAT) during the progression of obesity and diabetes. Intriguingly, subcutaneous adipose tissue (SAT) was spared from overt MCU fluctuations. Furthermore, MCU expression returned to physiological levels in VAT of patients after weight loss by bariatric surgery. Genetic manipulation of mitochondrial calcium uptake in 3T3-L1 adipocytes demonstrated that changes in mitochondrial calcium concentration ([Ca2+]mt) can affect mitochondrial metabolism, including oxidative enzyme activity, mitochondrial respiration, membrane potential, and reactive oxygen species formation. Finally, our data suggest a strong relationship between [Ca2+]mt and the release of IL-6 and TNFα in adipocytes. Altered mitochondrial calcium flux in fat cells may play a role in obesity and diabetes and may be associated with the differential metabolic profiles of VAT and SAT.

Incidence and Predictors of Hypoglycemia 1 Year After Laparoscopic Sleeve Gastrectomy.

INTRODUCTION: Hypoglycemia is a known adverse event following gastric bypass. The incidence of hypoglycemia after laparoscopic sleeve gastrectomy (LSG) is still under investigation. The aim of our study was to verify the presence of oral glucose tolerance test (OGTT)-related hypoglycemia after LSG and to identify any baseline predictors of its occurrence. METHODS: We analyzed 197 consecutive non-diabetic morbid obese patients that underwent LSG. All patients were studied before and 12 months after LSG. Evaluation included anthropometric parameters, 3-h OGTT for blood glucose (BG), insulin and c-peptide, lipid profile, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), highly sensitive C-reactive protein (hsCRP), and leptin. Hypoglycemia was defined as BG ≤ 2.7 mmol/l. RESULTS: After surgery, 180 patients completed the OGTT. Eleven patients did not complete the test for gastric intolerance, and in six patients, the test was stopped earlier for the onset of severe symptomatic hypoglycemia. Of the patients, 61/186 (32.8%) had at least one OGTT-related hypoglycemia. The highest frequency of hypoglycemic events occurred 150' after glucose load (20.2%). At baseline, patients with hypoglycemic events after surgery (Hypo) were younger (40 ± 11 vs 46 ± 10 years; p < 0.001), less obese (BMI 46 ± 5.7 vs 48.4 ± 7.9 kg/m2; p < 0.05), and had a worse lipid profile as compared to patients without hypoglycemic events (N-Hypo). Moreover, after LSG, Hypo patients compared with N-Hypo presented a higher weight loss (%EBMIL 80 ± 20 vs 62 ± 21%; p < 0.001). Low age, low fasting glucose, and high triglyceride levels before LSG were independent predictors of hypoglycemia development after surgery (r 2 = 0.131). CONCLUSION: These findings confirm the high incidence of post-prandial hypoglycemia 1 year after LSG. Hypoglycemia is more frequent in younger patients with lower fasting glucose and higher triglyceride levels before surgery.

Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery.

CONTEXT: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. OBJECTIVE: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and ß-cell function by mathematical modeling of the C-peptide response to glucose. RESULTS: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min-1 · m-2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min-1 · m-2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, ß-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min-1 · m2 · mM-1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. CONCLUSIONS: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better ß-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.