Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner

Abstract

Purpose We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4). Methods Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies. Results COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO. Conclusion Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4. Keywords Medium-chain fatty acids • Long-chain fatty acids • Coconut oil • Fatty acid binding protein 4 • Gastrointestinal motility • Irritable bowel syndrome Abbreviations CLA Conjugated LA COCO Coconut oil Ct * Jakub Fichna

Changes in Fatty Acid Dietary Profile Affect the Brain–Gut Axis Functions of Healthy Young Adult Rats in a Sex-Dependent Manner

“…We did not find any substantial changes in response to colonic distension associated with COCO and EP diets, compared with SOY diet, in either males or females, although both diets seemed to slightly reduce the duration of contractions in males and the frequency of contractions (particularly at low pressures) in females. Previous studies in male rodents have stablished that EP diet can increase the visceromotor response to colonic distension in mice [31] and reduce the response to the highest pressures in rats [30]. Differences regarding the time animals were fed on the different diets, or the methods used to perform the colonic distension, can contribute to the differences found across this and previous studies.…”

“…In this line, Mosińska et al used purified diets with 16% energy from fat and different FA composition (AIN-93G and two additional diets modified from it, one enriched in SFAs and the other one enriched in PUFAs) in male rats [30] and mice [31], but females were not studied. Furthermore, the effects of these diets on behavioral parameters relevant to the occurrence of IBS and comorbid chronic pain syndromes are unknown.…”

The microbiome in adolescents with irritable bowel syndrome and changes with percutaneous electrical nerve field stimulation

“…In contrast to these results, we found an increased abundance of a superpathway of fatty acid biosynthesis for long‐chain fatty acids (LCFA, including palmitoleic acid and cis‐vaccenic acid). There is evidence in preclinical models that LCFA can increase colonic visceral hypersensitivity and are related to neuroinflammation in chronic pain syndromes 41–43 . This suggests a potential role of LCFA in the pathophysiology of IBS.…”

“…There is evidence in preclinical models that LCFA can increase colonic visceral hypersensitivity and are related to neuroinflammation in chronic pain syndromes. [41][42][43] This suggests a potential role of LCFA in the pathophysiology of IBS.…”

Metabolomic, microbiome and transcriptomic study of crofelemer or loperamide in rat model of afatinib-induced intestine epithelial damage and diarrhea

“…Rather, Cdo1, Adipoq, Fabp4, cfd, Usp18, Oaslk, Trarg1 and Thrsp are genes that are commonly regulated by both crofelemer and loperamide. FABP4 and Adipoq are fatty acid regulating genes that are suggested to take a role in intestinal disorders and/or diarrhea (Mosińska et al, 2020;Mosińska et al, 2020). Such genes may regulate the process of TKIinduced diarrhea and are worthy of further investigations.…”