RESUMEN
BACKGROUND: Gut L-type enteroendocrine cells (EECs) are intestinal chemosensory cells that secrete satiety hormones GLP-1 and PYY in response to activation of G-protein coupled receptors (GPCRs) by luminal components of nutrient digestion and microbial fermentation. Regulator of G-protein Signaling (RGS) proteins are negative regulators of GPCR signaling. The expression profile of RGS in EECs, and their potential role in satiety hormone secretion and obesity is unknown. METHODS: Transcriptomic profiling of RGS was completed in native colonic EECs was completed using single-cell RNA sequencing (scRNA-Seq) in lean and obesity, and human jejunal EECs with data obtained from a publicly available RNAseq dataset (GSE114853). RGS validation studies were completed using whole mucosal intestinal tissue obtained during endoscopy in 61 patients (n = 42 OB, n = 19 Lean); a subset of patients' postprandial plasma was assayed for GLP-1 and PYY. Ex vivo human intestinal cultures and in vitro NCI-H716 cells overexpressing RGS9 were exposed to GLP-1 secretagogues in conjunction with a nonselective RGS-inhibitor and assayed for GLP-1 secretion. FINDINGS: Transcriptomic profiling of colonic and jejunal enteroendocrine cells revealed a unique RGS expression profile in EECs, and further within GLP-1+ L-type EECs. In obesity the RGS expression profile was altered in colonic EECs. Human gut RGS9 expression correlated positively with BMI and negatively with postprandial GLP-1 and PYY. RGS inhibition in human intestinal cultures increased GLP-1 release from EECs ex vivo. NCI-H716 cells overexpressing RGS9 displayed defective nutrient-stimulated GLP-1 secretion. INTERPRETATION: This study introduces the expression profile of RGS in human EECs, alterations in obesity, and suggests a role for RGS proteins as modulators of GLP-1 and PYY secretion from intestinal EECs. FUNDING: AA is supported by the NIH(C-Sig P30DK84567, K23 DK114460), a Pilot Award from the Mayo Clinic Center for Biomedical Discovery, and a Translational Product Development Fund from The Mayo Clinic Center for Clinical and Translational Science Office of Translational Practice in partnership with the University of Minnesota Clinical and Translational Science Institute.
Asunto(s)
Células Enteroendocrinas , Péptido 1 Similar al Glucagón , Obesidad , Péptido YY , Proteínas RGS , Transducción de Señal , Humanos , Células Enteroendocrinas/metabolismo , Obesidad/metabolismo , Proteínas RGS/metabolismo , Proteínas RGS/genética , Péptido 1 Similar al Glucagón/metabolismo , Péptido YY/metabolismo , Masculino , Femenino , Perfilación de la Expresión Génica , Transcriptoma , Adulto , Persona de Mediana Edad , Regulación de la Expresión Génica , Mucosa Intestinal/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genéticaRESUMEN
PURPOSE: Metabolic and bariatric surgery (MBS) could improve health-related quality of life (HrQoL) for selected patients with obesity. Although biliopancreatic diversion with duodenal switch (BPD-DS) is regarded as the most effective MBS technique in achieving weight loss, no consensus has been reached on the impact of BPD-DS on HrQoL. The aim of this meta-analysis is to assess the mid-term HrQoL after BPD-DS in the management of patients with obesity. MATERIALS AND METHODS: Cochrane, Embase, APA PsycInfo, PubMed, Scopus, and Web of Science were searched for articles from their inception to August 2022 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42022352073). RESULTS: From 223 studies screened, twelve studies met the eligibility criteria, with a total of 937 patients with obesity undergoing BPD-DS. Minimal clinically important differences (MCID) were reached for the physical component summary score (PCS) of the 36-Item Short-Form Health Survey (SF-36) (MD = 13.4) and impact of weight on quality of life (IWQOL)-Lite total score (MD = 48.7). Similarly, MCIDs were attained in the Laval questionnaire and SF-36 subscales. CONCLUSION: Our meta-analysis demonstrated an improvement in mid-term HrQoL after BPD-DS. Despite the promising trends demonstrated in this meta-analysis, further studies with large sample sizes are needed to evaluate the impact of HrQoL on patients with obesity after BPD-DS.