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The aim was to understand the direct impact of aerobic short-term exercise on lipid metabolism, specifically in regulating the mitochondrial carrier homolog 2 (MTCH2) and how it interferes with lipid metabolism in mesenteric adipose tissue. Swiss mice were divided into three groups: control, sedentary obese, and exercised obese. The obese groups were induced into obesity for fourteen weeks of a high-fat diet, and the trained submitted to seven aerobic exercise sessions. The exercise proved the significant increase of the pPerilipin-1, a hormone-sensitive lipase gene, and modulates lipid metabolism by increasing the expression of Mtch2 and acetyl Co-A carboxylase, perhaps occurring as feedback to regulate lipid metabolism in adipose tissue. In conclusion, we demonstrate, for the first time, how aerobic physical exercise increases Mtch2 transcription in mesenteric adipose tissue. This increase was due to changes in energy demand caused by exercise, confirmed by observing the significant reduction in mesenteric adipose tissue mass in the exercised group. Also, we showed that physical exercise increased the phosphorylative capacity of PLIN1, a protein responsible for the degradation of fatty acids in the lipid droplet, providing acyl and glycerol for cellular metabolism. Although our findings demonstrate evidence of MTCH2 as a protein that regulates lipid homeostasis, scant knowledge exists concerning the signaling of the MTCH2 pathway in regulatingfatty acid metabolism. Therefore, unveiling the means of molecular signaling of MTCH2 demonstrates excellent potential for treating obesity.
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Tejido Adiposo , Metabolismo de los Lípidos , Proteínas de Transporte de Membrana Mitocondrial , Obesidad , Condicionamiento Físico Animal , Animales , Ratones , Tejido Adiposo/metabolismo , Dieta Alta en Grasa/efectos adversos , Lípidos , Ratones Obesos , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Obesidad/metabolismo , Condicionamiento Físico Animal/fisiología , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiologíaRESUMEN
OBJECTIVES: Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn's disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. METHODS: In this study, patients with known or suspected Crohn's disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn's disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. RESULTS: A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn's disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn's disease (AUC = 0.93, p < 0.001). CONCLUSION: Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn's disease. CRITICAL RELEVANCE STATEMENT: Energy spectral parameters of creeping fat in Crohn's disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity. KEY POINTS: ⢠Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters. ⢠The creeping fat has distinct spectral parameters to normal mesenteric adipose. ⢠The spectral parameters accurately differentiate active and inactive Crohn's disease.
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BACKGROUND: Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence (POR) of Crohn's disease (CD). However, its prognostic value is uncertain, in part, due to difficulties studying it non-invasively. AIM: To evaluate the prognostic value of pre-operative radiographic mesenteric parameters for early endoscopic POR (ePOR). METHODS: We conducted a retrospective cohort study of CD subjects ≥ 12 years who underwent ileocecal or small bowel resection between 1/1/2007 to 12/31/2021 with computerized tomography abdomen/pelvis ≤ 6 months pre-operatively and underwent ileocolonoscopy ≤ 15 months post-operatively. Visceral adipose tissue (VAT) volume (cm3), ratio of VAT:subcutaneous adipose tissue (SAT) volume, VAT radiodensity, and ratio of VAT:SAT radiodensity were generated semiautomatically. Mesenteric lymphadenopathy (LAD, largest lymph node > 10 mm) and severe vasa recta (VR) engorgement (diameter of the VR supplying diseased bowel ≥ 2 × VR supplying healthy bowel) were derived manually. The primary outcome was early ePOR (Rutgeert's score ≥ i2 on first endoscopy ≤ 15 months post-operatively) and the secondary outcome was ePOR severity (Rutgeert's score i0-4). Regression analyses were performed adjusting for demographic and disease-related characteristics to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: Of the 139 subjects included, 45% of subjects developed early ePOR (n = 63). VAT radiodensity (aOR 0.59, 95%CI: 0.38-0.90) and VAT:SAT radiodensity (aOR 8.54, 95%CI: 1.48-49.28) were associated with early ePOR, whereas, VAT volume (aOR 1.23, 95%CI: 0.78-1.95), VAT:SAT volume (aOR 0.80, 95%CI: 0.53-1.20), severe VR engorgement (aOR 1.53, 95%CI: 0.64-3.66), and mesenteric LAD (aOR 1.59, 95%CI: 0.67-3.79) were not. Similar results were observed for severity of ePOR. CONCLUSION: VAT radiodensity is potentially a novel non-invasive prognostic imaging marker to help risk stratify CD patients for POR.
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Background: Prior to 2012, the mesentery was perceived as a fragmented structure, lacking distinct functional and anatomical characteristics, and was merely considered part of other digestive organs. Dr. J. Calvin Coffey's in 2012 in his study redefined the mesentery as a distinct organ with a clearly defined anatomical and histological structure, although its specific function remains under investigation. The continuous structure and unique tissue properties of the mesentery classify it as the 78th independent organ in the human body. Insights into mesenteric adipose tissue have enhanced our understanding of normal metabolic processes and disease etiology, impacting health significantly. Experimental and clinical research highlights the vital roles of visceral adipose tissue, influencing neighboring organ function. The interaction within the brain-gut-liver axis is illuminated by the newfound functions of mesenteric adipose tissue, emphasizing its independent organ status. Objective: This study aims to evaluate the latest findings on the structure and function of the mesentery, focusing on visceral-mesenteric adipose tissue, and assess its role as a new organ in the brain-gut-liver axis. Methods: A comprehensive analysis of clinical and experimental studies on the mesentery's structure and function was conducted, focusing on recent discoveries regarding mesenteric adipose tissue and its role in the brain-gut-liver axis. Results and Discussion: Recent research has revealed the mesentery's unique functions, particularly in mesenteric adipose tissue. Mesenteric adipose tissue plays a crucial role in metabolic functions and influences disease onset. It acts as a vital link in the brain-gut-liver axis, directly influencing hepatic metabolism and disorders such as metabolic syndrome. Conclusion: Scientific evidence confirms the mesentery's anatomical and functional specificities, solidifying its status as the 78th independent organ in the human body. It serves as a crucial link in the brain-mesentery-small intestine-liver axis, impacting health and disease. Ongoing research holds promise for advancing our understanding of pathophysiological mechanisms and treatment approaches for metabolic syndrome and other chronic diseases.
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Síndrome Metabólico , Humanos , Tejido Adiposo , Hígado , Mesenterio/metabolismo , EncéfaloRESUMEN
Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available studies are conflicting. It does, however, appear to negatively influence disease course whilst impacting on our medical and surgical therapies. The pro-inflammatory profile of the visceral adipose tissue might play a role in the pathogenesis and course of Crohn's Disease (CD). Interestingly, isolating the mesentery from the surgical anastomosis using a KONO-S technique significantly decreases anastomotic recurrence rate. Anti-obesity therapy is not widely used in IBD but was suggested as an adjunctive therapy in those patients. In this review, we aimed to highlight the epidemiology of obesity in IBD and to describe its influence on disease course and outcomes.
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Guanylyl cyclase C (GC-C) is a member of a family of enzymes that metabolize GTP to cGMP and was first identified as a receptor for heat-stable enterotoxin. Guanylin (GNY) has since been identified as an endogenous ligand for GC-C in the intestine of several mammalian species. The GNY/GC-C system regulates ion transportation and pH in the mucosa. Recently, it was reported that GC-C and GNY are involved in lipid metabolism in rat mesenteric adipose tissue macrophages. To examine the role of GC-C and GNY in lipid metabolism in cattle, we used a bovine mesenteric adipocyte primary culture system and a coculture system for bovine adipocytes and GNY-/GC-C-expressing macrophages. Fat droplets were observed to accumulate in bovine mesenteric adipocytes cultured alone, whereas few fat droplets accumulated in adipocytes indirectly cocultured with macrophages. We also observed that GC-C was present in bovine mesenteric adipose tissue, and that fat droplet accumulation decreased after in vitro GNY administration. Expressions of mRNAs encoding lipogenic factors decreased significantly in adipocytes after either coculture or GNY administration. These results suggest that the GNY/GC-C system is part of the control system for lipid accumulation in bovine mesenteric adipose tissue.