ArticleThe Journal of biological chemistry2011
Conjugated linoleic acids mediate insulin release through islet G protein-coupled receptor FFA1/GPR40.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 59 citations in OpenAlex.
- Multicolored sequential resonance energy transfer for detection of simultaneous ligand binding at G protein-coupled receptors.Nature communications · 2025Article
- The gut-derived metabolites as mediators of the effect of healthy nutrition on the brain.Frontiers in nutrition · 2023Review
- G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment.World journal of gastroenterology · 2021Review
- Point mutation of Ffar1 abrogates fatty acid-dependent insulin secretion, but protects against HFD-induced glucose intolerance.Molecular metabolism · 2017Article
- Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4.British journal of pharmacology · 2015Review
- Detection of free fatty acid receptor 1 expression: the critical role of negative and positive controls.Diabetologia · 2014Article
- Article
- Role of the lower and upper intestine in the production and absorption of gut microbiota-derived PUFA metabolites.PloS one · 2014Article
- Drugs or diet?--Developing novel therapeutic strategies targeting the free fatty acid family of GPCRs.British journal of pharmacology · 2013Review
- Conjugated linoleic acid reduces adiposity and increases markers of browning and inflammation in white adipose tissue of mice.Journal of lipid research · 2013Article
- Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes.Journal of lipid research · 2013Article
- Approaches for probing allosteric interactions at 7 transmembrane spanning receptors.Progress in molecular biology and translational science · 2013Review
- Article
- G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1.Diabetologia · 2012Article
- Cross-sectional study of conjugated linoleic acid in adipose tissue and risk of diabetes.The American journal of clinical nutrition · 2012Article
- Conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells is mediated by both G protein coupled receptor-dependent activation of the AMP-activated protein kinase pathway and by oxidative stress.Cellular signalling · 2011Article
- Applying label-free dynamic mass redistribution technology to frame signaling of G protein-coupled receptors noninvasively in living cells.Nature protocols · 2011Article
- Drug discovery opportunities and challenges at g protein coupled receptors for long chain free Fatty acids.Frontiers in endocrinology · 2011Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1-/- knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.