Extracellular vesicle signature is associated with cardio-metabolic improvement after bariatric surgery.

Aims: Bariatric surgery (BS) reduces obesity-associated systemic inflammation leading to multiple cardiovascular (CV) and metabolic benefits. Here, we tested whether measuring vaso-inflammatory cytokines, gut hormones, and circulating extracellular vesicles (EV) provide vaso-inflammatory-metabolic signatures that better correlate to CV-metabolic outcomes after BS, compared to a standard clinical assessment including body weight (BW) loss and traditional CV risk factors.

Methods: In 111 patients with severe obesity, conventional clinical-biochemical parameters and non-conventional vaso-inflammatory-metabolic markers were analyzed at baseline, after 1- (T12) and 3-years (T36) post-BS and were associated to post-surgical BW loss and improvement of patients' CV-metabolic profile.

A cell atlas to guide research into appetite control.

An atlas of all the cell types in the dorsal vagal complex of rodents will help neuroscientists seeking to understand appetite and researchers working to design better drugs for the treatment of obesity and related disorders.

Acute High-Altitude Exposure Increases Transcription of Tricarboxylic Acid Cycle Enzymes in Human Duodenal Biopsies.

A recent study of our group quantifying C-octanoate metabolism in HA (Capanna Margherita [MG]/4,559 m) showed that acute HA exposure might lead to an increase of the lipolytic and CO-producing pathways. To further test this hypothesis, we investigated intestinal biopsies from the same participants from simultaneously performed endoscopy studies for changes of mRNA-expression levels of the beta-oxidation enzymes and the decarboxylating tricarboxylic acid cycle (TCA) enzymes. Duodenal biopsies of 16 subjects exposed to HA were sampled via gastro-duodenoscopy at Zurich (baseline ZH, 490 m), on day 2 (MG2) and on day 4 at HA (MG4).

Ghrelin's role in regulating food intake among inpatients at nutritional risk: A secondary analysis of the randomized clinical trial EFFORT.

Background: Ghrelin is an orexigenic hormone that stimulates food intake by hypothalamic actions. There is limited data on its circulating levels, pathophysiological role, and prognostic and therapeutic potential in disease-related malnutrition.

Methods: We investigated via this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) the association of admission ghrelin levels in terms of malnutrition phenotype, nutritional target achievement, and treatment response.

Exposure to high-energy diet reduces cue-evoked dopamine in obesity-resistant but not obesity-prone female rats.

The mesolimbic dopamine system is a critical neural pathway that contributes to reward processing and motivation through the release of dopamine in the nucleus accumbens (NAc) from neurons originating in the ventral tegmental area. Various factors, like intake of palatable foods and obesity, can alter dopamine release and subsequent behaviors. In this study, using a polygenic rat model of obesity, we investigated if the mesolimbic dopamine system responds differently after exposure to high-energy (HE) diet in female rats that are obesity-prone (DIO) or obesity-resistant (DR).

Role of amylin in feeding and satiation.

This article summarizes the key literature describing the effects of the pancreatic beta-cell hormone amylin on eating. One of the first described and best investigated effects of amylin on eating is its physiological effect to control meal size by inducing satiation. This effect is very rapid, short-lasting and probably directly reflects the meal-induced increase in circulating amylin levels.

Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.

Background: Amylin (AmyR) and calcitonin (CTR) receptor co-agonists are currently in Phase II/III clinical trials for obesity treatment. Amylin binds to a heterodimeric receptor composed of CTR and the receptor activity modifying proteins 1, 2 or 3 (RAMP1-3).

Methods: We investigated the role of amylin 1 and 3 (AMYR, AMYR) receptors in modulating the pharmacological effects of the dual amylin-calcitonin receptor agonists, cagrilintide and salmon calcitonin (sCT), in RAMP1/3 knockout (KO) mice.

High Dietary Cation and Anion Difference Enhanced Renal Response to an Acute Acid Load of Lactating Goat Fed Under Tropical Conditions.

High ambient temperature (HTa) in tropical conditions leads to evaporative heat dissipation by panting in lactating dairy goats. This panting causes respiratory hypocapnia, which increases the renal excretion of buffer molecules including sodium, potassium, and bicarbonate. In response, renal acid excretion decreases to preserve acidity.

A Western-Style Diet Influences Ingestive Behavior and Glycemic Control in a Rat Model of Roux-en-Y Gastric Bypass Surgery.

: Roux-en-Y gastric bypass (RYGB) surgery results in weight reduction and decreased energy intake and can ameliorate type 2 diabetes. These beneficial effects are usually attributed to changes in hunger and satiety and relatively rapid improvements in glycemic control, but these effects may depend on dietary adherence. The aim of this study is to investigate the relatively early effects of RYGB surgery on weight reduction (by focusing on eating patterns) and glycemic control in rats subjected to a healthy maintenance diet or an unhealthy Western-style diet.

Comparison of the inflammatory biomarkers IL- 6, TNF-α, and CRP to predict the effect of nutritional therapy on mortality in medical patients at risk of malnutrition : A secondary analysis of the randomized clinical trial EFFORT.

Background: Inflammation is a key driver of disease-related malnutrition and patients with high inflammation may not show the same benefits from nutritional therapy as other patients. We compared in an exploratory manner the prognostic ability of interleukin- 6 (IL- 6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) to predict outcome and response to nutritional therapy, respectively, within a large cohort of patients from a previous nutritional trial.

Methods: This is a secondary analysis of the Swiss-wide, multicenter, randomized controlled Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) trial comparing individualized nutritional support with usual care nutrition in medical inpatients.

A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.

Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem.

The (dys)regulation of energy storage in obesity.

Metabolic energy stored mainly as adipose tissue is homeostatically regulated. There is strong evidence that human body weight (BW) is physiologically regulated, i.e.

Novel neural pathways targeted by GLP-1R agonists and bariatric surgery.

The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide has revolutionized the treatment of obesity, with other gut hormone-based drugs lined up that show even greater weight-lowering ability in obese patients. Nevertheless, bariatric surgery remains the mainstay treatment for severe obesity and achieves unparalleled weight loss that generally stands the test of time. While their underlying mechanisms of action remain incompletely understood, it is clear that the common denominator between GLP-1R agonists and bariatric surgery is that they suppress food intake by targeting the brain.

The processing intermediate of human amylin, pro-amylin(1-48), has in vivo and in vitro bioactivity.

Amylin is released by pancreatic beta-cells in response to a meal and its major soluble mature form (37 amino acid-peptide) produces its biological effects by activating amylin receptors. Amylin is derived from larger propeptides that are processed within the synthesizing beta-cell. There are suggestions that a partially processed form, pro-amylin(1-48) is also secreted.

Mammalian models of diabetes mellitus, with a focus on type 2 diabetes mellitus.

Although no single animal model replicates all aspects of diabetes mellitus in humans, animal models are essential for the study of energy balance and metabolism control as well as to investigate the reasons for their imbalance that could eventually lead to overt metabolic diseases such as type 2 diabetes mellitus. The most frequently used animal models in diabetes mellitus research are small rodents that harbour spontaneous genetic mutations or that can be manipulated genetically or by other means to influence their nutrient metabolism and nutrient handling. Non-rodent species, including pigs, cats and dogs, are also useful models in diabetes mellitus research.

Obesity-induced changes in gene expression in feline adipose and skeletal muscle tissue.

Indoor-confined cats are prone to developing obesity due to a sedentary life and an energy intake exceeding energy requirements. As in humans, feline obesity decreases insulin sensitivity and increases the risk of developing feline diabetes mellitus, but the pathophysiological mechanisms are currently poorly understood. Human obesity-related metabolic alterations seem to relate to changes in the expression of genes involved in glucose metabolism, insulin action and inflammation.