Long-chain fatty acid sensing in the gastrointestinal tract

McLaughlin, John

doi:10.1042/bst0351199

Cited by 16 publications

(10 citation statements)

References 46 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The length of the fatty acid carbon chain also determines CCK release. Most research studies have shown that fatty acids with an acyl chain length < 10 carbon atoms do not induce CCK secretion in humans, whereas long-chain fatty acids with at least 12 carbons are the most potent stimulants of CCK (48,62). The sensing mechanism by which I cells detect long-chain fatty acids and trigger CCK secretion has long been associated with GPR.…”

Section: Cells and Cckmentioning

confidence: 98%

Diet: Friend or Foe of Enteroendocrine Cells: How It Interacts with Enteroendocrine Cells

Morán-Ramos

Tovar

Torres

2012

Advances in Nutrition

View full text Add to dashboard Cite

Gut hormones play a key role in the regulation of food intake, energy expenditure, glucose homeostasis, lipid metabolism, and a wide range of metabolic functions in response to food ingestion. These hormones are altered in metabolic diseases, such as obesity and type 2 diabetes, and are thus proposed to be possible targets for the prevention or treatment of these diseases. It is clear that food composition, macronutrients, and other non-nutrient components as well as the physical properties of food not only modulate the secretion of gut peptides but also modulate transcription and enteroendocrine cell differentiation, which ultimately modifies gut hormone response. The specific mechanisms or sensing machinery that respond to the different components of the diet have been studied for many years; however, over the last few years, new molecular genetic techniques have led to important advances, thereby allowing a deeper understanding of these mechanisms. This review addresses the current knowledge regarding enteroendocrine cells and how diet interacts with this machinery to stimulate and regulate the secretion of gut peptides. The potential for diet interventions as a promising strategy for modulating gut hormone responses to food ingestion and, ultimately, preventing or treating metabolic diseases is being emphasized considering that these diseases are currently a public health burden.

show abstract

Section: Cells and Cckmentioning

confidence: 98%

Diet: Friend or Foe of Enteroendocrine Cells: How It Interacts with Enteroendocrine Cells

Morán-Ramos

Tovar

Torres

2012

Advances in Nutrition

View full text Add to dashboard Cite

show abstract

“…More precisely, they do not address whether the ‘physiological’ mode of delivering dietary lipids to the apical pole of enterocytes as complex micelles, known to be critical for intestinal lipid intake [10], is required to induce the effects reported. While some mechanisms by which enteroendocrine cells sense lipids have been described [11], it is not known whether enterocytes sense dietary lipids. Previous works from our group indicated that there is some sensing of micellar dietary lipids by enterocytes as they demonstrated that the apical supply of postprandial micelles (mimicking those present in the intestinal lumen in vivo after a meal) induced specific effects in Caco-2/TC7 cells, a model reproducing in culture most of the morphological and functional characteristics of enterocytes [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1

et al. 2009

View full text Add to dashboard Cite

BackgroundThe intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion.Methodology/Principal FindingsThe effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation.Conclusions/SignificanceThese results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway.

show abstract

“…Several G-protein–coupled receptors (GPRs) have been identified as fatty acid sensors with nutrient-sensing capabilities by endocrine cells 6,7 ; in particular, the LCFA receptors GPR40 and GPR120 have been suggested as possible nutrient detectors mediating CCK secretion. 8,9 …”

mentioning

confidence: 99%

The G-Protein−Coupled Receptor GPR40 Directly Mediates Long-Chain Fatty Acid−Induced Secretion of Cholecystokinin

et al. 2011

View full text Add to dashboard Cite

BACKGROUND & AIMS Long-chain fatty acid receptors G-protein–coupled receptor 40 (GPR40) (FFAR1) and GPR120 have been implicated in the chemosensation of dietary fats. I cells in the intestine secrete cholecystokinin (CCK), a peptide hormone that stimulates digestion of fat and protein, but these cells are rare and hard to identify. We sought to determine whether dietary fat-induced secretion of CCK is directly mediated by GPR40 expressed on I cells. METHODS We used fluorescence-activated cell sorting to isolate a pure population of I cells from duodenal mucosa in transgenic mice that expressed green fluorescent protein under the control of the CCK promoter (CCK–enhanced green fluorescent protein [eGFP] bacterial artificial chromosome mice). CCK-eGFP cells were evaluated for GPR40 expression by quantitative reverse transcription polymerase chain reaction and immunostaining. GPR40−/− mice were bred with CCK-eGFP mice to evaluate functional relevance of GPR40 on long-chain fatty acid–stimulated increases in [Ca2+]i and CCK secretion in isolated CCK-eGFP cells. Plasma levels of CCK after olive oil gavage were compared between GPR40+/+ and GPR40−/− mice. RESULTS Cells that expressed eGFP also expressed GPR40; expression of GPR40 was 100-fold greater than that of cells that did not express eGFP. In vitro, linoleic, oleic, and linolenic acids increased [Ca2+]i; linolenic acid increased CCK secretion by 53% in isolated GPR40+/+ cells that expressed eGFP. In contrast, in GPR40−/− that expressed eGFP, [Ca2+]i response to linoleic acid was reduced by 50% and there was no significant CCK secretion in response to linolenic acid. In mice, olive oil gavage significantly increased plasma levels of CCK compared with pregavage levels: 5.7-fold in GPR40+/+ mice and 3.1-fold in GPR40−/− mice. CONCLUSIONS Long-chain fatty acid receptor GPR40 induces secretion of CCK by I cells in response to dietary fat.

show abstract

Long-chain fatty acid sensing in the gastrointestinal tract

Cited by 16 publications

References 46 publications

Diet: Friend or Foe of Enteroendocrine Cells: How It Interacts with Enteroendocrine Cells

Diet: Friend or Foe of Enteroendocrine Cells: How It Interacts with Enteroendocrine Cells

Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1

The G-Protein−Coupled Receptor GPR40 Directly Mediates Long-Chain Fatty Acid−Induced Secretion of Cholecystokinin

Contact Info

Product

Resources

About