title: Intestinal permeability is associated with visceral adiposity in healthy women.
abstract: Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. anders.gummesson@astrazeneca.com
authors.forename: Anders
authors.initials: A
authors.lastname: Gummesson
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Len H
authors.initials: LH
authors.lastname: Storlien
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.forename: Pål
authors.initials: P
authors.lastname: Lundin
authors.forename: Lars
authors.initials: L
authors.lastname: Löfgren
authors.forename: Kaj
authors.initials: K
authors.lastname: Stenlöf
authors.forename: Yan Y
authors.initials: YY
authors.lastname: Lam
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D015331:Cohort Studies; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism / Q000503:physiopathology; D050151:Subcutaneous Fat / Q000378:metabolism; D059349:Urine Specimen Collection; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D007328:Insulin