Metabolic surgery

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (https://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas...

BACKGROUND: The correlation between resected gastric volume (RGV) and neuro-humoral changes (ghrelin and GLP-1) after laparoscopic sleeve gastrectomy (LSG) and their effects on type 2 diabetes mellitus (T2DM) has been evaluated. MATERIALS: Ninety-eight patients were divided in two groups: RGV <1200 mL (group A: 53 pts) and RGV >1200 mL (group B: 45 pts). Insulin secretion (insulin area under the curve (AUC)), insulinogenic index (IGI) and insulin-resistance (homeostasis model assessment, HOMAIR ) were assessed before and after surgery (at the 3rd day and 6, 12 and 24 months after LSG) using the oral glucose tolerance test (OGTT)...

Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated...

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation...

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning with fibrosis in severe cases, and high prevalence in obesity. We aimed at defining NASH signature in morbid obesity by mass spectrometry-based lipidomic analysis. METHODS: We analyzed systemic blood before and 12 months after bariatric surgery, along with portal blood and adipose tissue lipid efflux collected from obese women at the time of surgery (9 structural classes, 150 species)...

PURPOSE OF REVIEW: To describe the recent advances in our understanding of fatty acids and lipids in paediatric nonalcoholic fatty liver disease (NAFLD) and their future implications. RECENT FINDINGS: Data have been accumulated to suggest that ceramides are the main drivers of hepatic insulin resistance in NAFLD, and inhibition of ceramide synthesis improves histology in mice.Saturated fatty acids formed by de novo lipogenesis generate increased lipotoxicity compared with dietary-derived saturated fatty acids...

Bariatric surgeries, such as Roux-en-Y gastric bypass and vertical sleeve gastrectomy, produce significant and durable weight loss in both humans and rodents. Recently, these surgical interventions have also been termed metabolic surgery because they result in profound metabolic improvements that often surpass the expected improvement due to body weight loss alone. In this review we focus on the weight-loss independent effects of bariatric surgery, which encompass energy expenditure and macronutrient preference, the luminal composition of the gut (i...

BACKGROUND: Robust data on quality of life (QoL) after different techniques of bariatric surgery are sparse. This RCT compared excess weight loss (EWL) and QoL after sleeve gastrectomy versus Roux-en-Y gastric bypass (RYGB). METHODS: Obese patients were assigned randomly to RYGB or sleeve gastrectomy. The primary outcome measure was EWL. Secondary outcomes included QoL, co-morbidity, adverse events, vitamin and glycolipid status. QoL was assessed before and annually after surgery, using the Moorehead-Ardelt Quality of Life Questionnaire II (M-A-QoLQII) and Gastrointestinal Quality of Life Index (GIQLI)...

Obesity is one of the most important public health conditions worldwide. Bariatric surgery for severe obesity is an effective treatment that results in the improvement and remission of many obesity-related comorbidities, as well as providing sustained weight loss and improvement in quality of life. Contemporary bariatric operations include Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric band and the duodenal switch. The vast majority of these procedures are now performed using laparoscopic technique, the main advantages of which include rapid recovery, the reduction of postoperative pain and the reduction of wound-related complications, compared with open surgery...

BACKGROUND/OBJECTIVES: Liquid fructose associates with prevalence of type 2 diabetes mellitus and obesity. Intervention studies suggest that metabolically unfit individuals are more responsive than healthy individuals to liquid fructose. We determined whether mice consuming an obesogenic Western diet were more responsive than chow-fed mice to the alterations induced by liquid fructose supplementation (LFS). METHODS: C57BL/6N mice were fed chow or Western diet±ad libitum 15% fructose solution for 12 weeks...

BACKGROUND: Food cues are omnipresent and may trigger overconsumption. In the past 2 decades, the prevalence of childhood obesity has increased dramatically. Because children's brains are still developing, especially in areas important for inhibition, children may be more susceptible than adults to tempting food cues. OBJECTIVE: We examined potential developmental differences in children's and adults' responses to food cues to determine how these responses relate to weight status...

Obesity is associated with a variety of medical conditions such as type 2 diabetes and cardiovascular diseases and is therefore responsible for high morbidity and mortality rates. Increasing energy expenditure by brown adipose tissue (BAT) is a current novel strategy to reduce the excessive energy stores in obesity. Brown adipocytes burn energy to generate heat and are mainly activated upon cold exposure. As prolonged cold exposure is not a realistic therapy, researchers worldwide are searching for novel ways to activate BAT and/or induce beiging of white adipose tissue...

Nonalcoholic steatohepatitis (NASH) affects 2%-3% of the US population and is expected to become the leading indication for liver transplantation in the next decade. Bariatric surgery may be an effective but expensive treatment for NASH. Using a state-transition model, our analysis assessed the effectiveness and cost-effectiveness of surgery to manage NASH. We simulated the benefits and harms of laparoscopic Roux-en-Y gastric bypass surgery in patients defined by weight class (overweight, mild obesity, moderate obesity, and severe obesity) and fibrosis stage (F0-F3)...

Nonalcoholic fatty liver disease (NAFLD) is a disease of attention because of increase in prevalence from 20% to 41%. The clinical and pathological conditions in patients with NAFLD range from steatosis alone to nonalcoholic steatohepatitis (NASH) with or without fibrosis to hepatic cancer. In the United States, NAFLD was the second-leading indication for liver transplant between 2004 and 2013. Although imaging studies such as magnetic resonance elastography and the use of diagnostic panels and scoring systems can provide a fairly accurate diagnosis of NAFLD, there are few treatment options for patients with mild to moderate disease other than lifestyle modification...

BACKGROUND: Several recent studies have shown a strong association between non-alcoholic steatohepatitis (NASH) and chronic kidney disease. AIM: To examine the relationship between changes in liver histology and renal function in patients with NASH. METHODS: The present analysis represents a post hoc analysis of a recently published trial that included 261 patients with NASH who were treated with lifestyle modifications during 52 weeks. Kidney function was evaluated through Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rates (eGFR, mL/min/1...

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Studies on experimental animals with knockout of the insulin receptor gene Insr (in the whole body or in certain tissues) and/or related genes encoding proteins involved in realization of insulin signal transduction in target cells, have made an important contribution to the elucidation of insulin regulation of metabolism, particularly fat metabolism. Since the whole insulin secreted by b-cells, together with the products of gastrointestinal tract digestion of proteins, fats, and carbohydrates reach the liver, the latter is the first organ on which this hormone acts...

Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis...

Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D), induces insulin resistance in peripheral insulin target tissues. Several mechanisms have been identified related to cross-talk between adipose tissue, skeletal muscle and liver. These mechanisms involve both increased free fatty acid release and altered secretion of adipokines from adipose tissue. A major determinant of metabolic health is the ability of subcutaneous adipose tissue (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots including liver (i...

OBJECTIVE: To determine whether bariatric surgery is effective for the treatment of nonalcoholic steatohepatitis (NASH) in adolescence, we compared the efficacy of laparoscopic sleeve gastrectomy (LSG) with that of lifestyle intervention (nonsurgical weight loss [NSWL]) for NASH reversal in obese adolescents. STUDY DESIGN: Obese (body mass index ≥ 35 kg/m2 ) adolescents (13-17 years of age) with biopsy-proven NAFLD underwent LSG, lifestyle intervention plus intragastric weight loss devices (IGWLD), or only NSWL...