Improvement of Low-Grade Inflammation in Patients with Metabolically Healthy Severe Obesity After Primary Bariatric Surgery.

INTRODUCTION: The inflammatory state that accompanies adiposity and the metabolic syndrome (MetS) is called "low-grade" inflammation. White blood cell count (WBC) has been proposed as an emerging biomarker for predicting future cardiovascular events, MetS and mortality. Bariatric surgery (BS) improves comorbidities associated with obesity and the MetS and the surgically induced weight loss is known to improve inflammatory status. OBJECTIVES: To analyze the improvement of low-grade inflammation associated to obesity in patients with metabolically healthy severe obesity (MHSO) and patients with metabolically unhealthy obesity (MUSO) (severe obesity with MetS) after primary bariatric surgery as well as the protective effect of BS against the development of MetS in patients with MHSO by reducing the WBC. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients undergoing laparoscopic primary BS (gastric by-pass or sleeve gastrectomy) from January 2004-December 2015. Outcomes included changing of low-grade inflammation in terms of leukocytes, neutrophils, lymphocytes, and platelets. RESULTS: Twenty-one patients with MHSO and 167 patients with MUSO underwent laparoscopic primary BS. The preoperative values of leukocyte and platelet were statistically higher in the group of patients with MHSO. In both groups, there was significant postoperative decrease of inflammatory markers. The greatest drop in WBC occurred in the second postoperative year. No patient of the group of patients with MHSO developed MetS within five postoperative years. CONCLUSIONS: Surgically induced weight loss plays an important role for improvement in chronic inflammation associated to obesity because of reduction of visceral fat mass. MHSO associates a low-grade chronic inflammatory status comparable to MUSO. The improvement or decrease of low-grade inflammation in patients with metabolically healthy severe obesity after bariatric surgery could have a protective effect against the development of MetS and medical conditions associated with severe obesity.

Metabolically Healthy Obesity and Bariatric Surgery.

A peculiar category of persons with obesity lacking common metabolic disturbances has been depicted and termed as metabolically healthy obesity (MHO). Yet, although MHO patients are free of obesity-associated complications, they might not be entirely precluded from developing cardio-metabolic disorders. Among patients with morbid obesity (MO) who are referred to bariatric surgery, a subset of metabolically healthy MO (MHMO) has been identified and the question arises if these patients would benefit from surgery in terms of mitigating the peril of cardio-metabolic complications. We revisited the pathophysiological mechanisms that define MHO, the currently available data on the cardio-metabolic risk of these patients and finally we reviewed the benefits of bariatric surgery and the urge to better characterize MHMO before submission to surgery.

Patients with clinically metabolically healthy obesity are not necessarily healthy subclinically: further support for bariatric surgery in patients without metabolic disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized. OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity. SETTING: A tertiary, academic, referral hospital. METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD. RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis. CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.

New obesity classification criteria as a tool for bariatric surgery indication.

Obesity plays relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional, and metabolic factors. Due to the role of adipose tissue in lipid and glucose metabolism, and low grade inflammation, it is necessary to classify obesity on the basis of body fat composition and distribution, rather than the simply increase of body weight, and the Body Mass Index. The new term of adiposopathy (''sick fat'') clearly defines the pathogenic role of adipose tissue. Four phenotypes of obese individuals have been described: (1) normal weight obese (NWO); (2) metabolically obese normal weight; (3) metabolically healthy obese; and (4) metabolically unhealthy obese or "at risk" obese. Moreover, sarcopenic obesity has been related to all the phenotypes. The category of normal weight lean, represented by metabolically healthy normal weight has been classified to distinguish from NWO. It is crucial to recommend a bariatric surgery taking into account adiposopathy and sick fat that occurs with the expansion of fat mass, changing the inflammatory and metabolic profile of the patient. Body fat percentage and genetic polymorphism have to be evaluated to personalize the best bariatric surgery intervention.

Morbidly "Healthy" Obese Are Not Metabolically Healthy but Less Metabolically Imbalanced Than Those with Type 2 Diabetes or Dyslipidemia.

BACKGROUND: We have investigated the differences between metabolically "healthy" morbidly obese patients and those with comorbidities. MATERIALS AND METHODS: Thirty-two morbidly obese patients were divided by the absence ("healthy": DM-DL-) or presence of comorbidities (dyslipidemic: DM-DL+, or dyslipidemic and with type 2 diabetes: DM+DL+). We have studied various plasma parameters and gene expression adipose tissue, before and after gastric bypass. RESULTS: The group DM+DL+ tends to have lower values than the other two groups for anthropometric parameters. Regarding the satiety parameters, only leptin (p = 0.0024) showed a significant increase with comorbidities. Lipid parameters showed significant differences among groups, except for phospholipids and NEFA. For insulin resistance parameters, only glucose (p < 0.0001) was higher in DM+DL+ patients, but not insulin or homeostasis model assessment of insulin resistance (HOMA-IR). The gene expression of adiponectin, insulin receptor (INSR) and glucose receptor-4 (GLUT4), in the subcutaneous fat, decreased in all groups vs. a non-obese control. Interleukin-6 (IL6) and the inhibitor of plasminogen activator type 1 (PAI-1) genes decreased only in DM-DL+ and DM+DL+, but not in "healthy" patients. Leptin increased in all groups vs. the non-obese control. The visceral fat from DM+DL+ patients showed a sharp decrease in adiponectin, GLUT4, IL6 and PAI-1. All parameters mentioned above improved very significantly by surgery, independent of the occurrence of comorbidities. CONCLUSIONS: The morbidly obese "healthy" individual is not really metabolically healthy, but morbidly obese individuals with diabetes and dyslipidemia are more metabolically imbalanced.