Gut HIF2α signaling is increased after VSG, and gut activation of HIF2α decreases weight, improves glucose, and increases GLP-1 secretion.

Gastric bypass and vertical sleeve gastrectomy (VSG) remain the most potent and durable treatments for obesity and type 2 diabetes but are also associated with iron deficiency. The transcription factor HIF2α, which regulates iron absorption in the duodenum, increases following these surgeries. Increasing iron levels by means of dietary supplementation or hepatic hepcidin knockdown does not undermine the effects of VSG, indicating that metabolic improvements following VSG are not secondary to lower iron levels.

Vertical sleeve gastrectomy increases duodenal Lactobacillus spp. richness associated with the activation of intestinal HIF2α signaling and metabolic benefits.

Objective: Vertical Sleeve Gastrectomy (VSG) is one of the most efficacious treatments for obesity and its comorbidities. Although a range of evidence suggests that alterations of the microbiota in the distal gut following VSG are pivotal to these metabolic improvements, the effect of surgery to alter the microbiota of the proximal intestine and its effect on host physiology remain largely unknown. As the main bacteria in the upper small intestine, Lactobacillus subspecies have been appreciated as important regulators of gut function.

Intestinal HIF-2α Regulates GLP-1 Secretion via Lipid Sensing in L-Cells.

Background & Aims: Compelling evidence shows that glucagon-like peptide-1 (GLP-1) has a profound effect in restoring normoglycemia in type 2 diabetic patients by increasing pancreatic insulin secretion. Although L-cells are the primary source of circulating GLP-1, the current therapies do not target L-cells to increase GLP-1 levels. Our study aimed to determine the molecular underpinnings of GLP-1 secretion as an impetus to identify new interventions to target endogenous L-cells.

The Role of Elevated Branched-Chain Amino Acids in the Effects of Vertical Sleeve Gastrectomy to Reduce Weight and Improve Glucose Regulation.

Elevated levels of branched-chain amino acids (BCAAs) and their metabolites are strongly positively associated with obesity, insulin resistance, and type 2 diabetes. Bariatric surgery is among the best treatments for weight loss and associated morbidities. Clinical studies have reported that bariatric surgery decreases the circulating levels of BCAAs.

Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis.

Background: Animal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and drug discovery. Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a model of fibrosing NASH. The present study directly assessed the clinical translatability of the model by head-to-head comparison of liver biopsy histological and transcriptome changes in GAN DIO-NASH mouse and human NASH patients.

Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats.

Objective: Post-bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication.

Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr neurons decreased food intake and body weight but (unlike neighboring Cck cells) failed to promote aversion, revealing that Calcr neurons mediate a non-aversive suppression of food intake.

G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.

Bariatric surgeries are integral to the management of obesity and its metabolic complications. However, these surgeries cause bone loss and increase fracture risk through poorly understood mechanisms. In a mouse model, vertical sleeve gastrectomy (VSG) caused trabecular and cortical bone loss that was independent of sex, body weight, and diet, and this loss was characterized by impaired osteoid mineralization and bone formation.

The Unconventional Role for Gastric Volume in the Response to Bariatric Surgery for Both Weight Loss and Glucose Lowering.

Objective: To study the relationship between the amount of surgery-induced gastric volume reduction and long-term weight loss and glucose tolerance.

Background Data: Vertical sleeve gastrectomy (VSG) has recently surpassed gastric bypass to become the most popular surgical intervention to induce sustained weight loss. Besides inducing significant weight loss, VSG also improves glucose tolerance.

Metabolic comparison of one-anastomosis gastric bypass, single-anastomosis duodenal-switch, Roux-en-Y gastric bypass, and vertical sleeve gastrectomy in rat.

Background: One-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal switch (SADS) have become increasingly popular weight loss strategies. However, data directly comparing the effectiveness of these procedures with Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (SG) are limited.

Objectives: To examine the metabolic outcomes of OAGB, SADS, RYGB, and SG in a controlled rodent model.

Effects of sleeve gastrectomy on the composition and diurnal oscillation of gut microbiota related to the metabolic improvements.

Background: Disruptions of the composition and diurnal oscillation of gut microbiota are involved in metabolic disorders.

Objectives: To identify alterations in both the composition and diurnal oscillation of gut microbiota after high-fat diet (HFD) feeding and sleeve gastrectomy (SG) related to host metabolic status.

Setting: University laboratories.

Roman high and low avoidance rats differ in their response to chronic olanzapine treatment at the level of body weight regulation, glucose homeostasis, and cortico-mesolimbic gene expression.

Olanzapine, an antipsychotic agent mainly used for treating schizophrenia, is frequently associated with body weight gain and diabetes mellitus. Nonetheless, studies have shown that not every individual is equally susceptible to olanzapine's weight-gaining effect. Therefore, Roman high and low avoidance rat strains were examined on their responsiveness to olanzapine treatment.

The Physiology and Molecular Underpinnings of the Effects of Bariatric Surgery on Obesity and Diabetes.

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.

A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers.

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest.

The lateral hypothalamus: a site for integration of nutrient and fluid balance.

This paper reviews seemingly obligatory relations between nutrient and fluid balance. A relatively novel neuronal pathway involving interplay between acetylcholine and the melanocortins, αMSH and AGRP in the arcuate nucleus (Arc) of the hypothalamus projecting to the lateral hypothalamus (LH) may bridge this gap. In the fasted condition, increased expression of MCH (due to muscarinic-3 receptor stimulation and low melanocortin tone) and neuronal release of MCH (via Orexin signaling) underlies a drive towards positive energy balance, increased B cell capacity to secrete insulin, and this is associated with optimal fluid homeostasis.

Olanzapine affects locomotor activity and meal size in male rats.

Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect. To investigate how olanzapine affects different aspects of energy balance, we used male rats to determine effects on meal patterns, food preference, locomotor activity and body temperature. In two short-term experiments olanzapine was administered via osmotic minipumps.