CD36, but not GPR120, is required for efficient fatty acid utilization during endurance exercise

Fujitani, Mina; Matsumura, Shigenobu; Masuda, Daisuke; Yamashita, Shizuya; Fushiki, Tohru; Inoue, Kazuo

doi:10.1080/09168451.2014.940835

Cited by 14 publications

(13 citation statements)

References 34 publications

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“…CD36-knockout mice (C57BL6/J background) (16) were provided as previously described (8). Wild-type and CD36-knockout littermates were obtained from the same breeding pair and thus have a genetically identical background.…”

Section: Methodsmentioning

confidence: 99%

A role of CD36 in the perception of an oxidised phospholipid species in mice

et al. 2015

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CD36 is a broadly expressed transmembrane protein that engages multiple ligands, including polar lipids. This protein is thought to even contribute to the chemosensory detection of long-chain fatty acids in the oral cavity of rodents. In this study, we assessed whether animals consciously perceive a ligand of CD36, 1-(palmitoyl)-2-(5-keto-6-octanedioyl)phosphatidylcholine (KOdiA-PC), and if so, whether CD36 is involved in sensing the oxidised phospholipid species. We found that mice avoided or hesitated to ingest fluids containing KOdiA-PC, suggesting a conscious perception of the lipid in the animals. We assessed the involvement and role of CD36 in the KOdiA-PC perception by comparing the behavioural responses of wild-type and CD36-deficient mice to the test fluids, and provided evidence that the protein could play a role in sensing a lower level of the lipid. We also found that transection of the olfactory nerve of wild-type mice resulted in an inability to perceive KOdiA-PC, suggesting the significance of olfactory system in the lipid sensing. Our findings, coupled with the recent finding of CD36 expression in the mouse olfactory epithelium, led us to predict that the site of CD36 action in the KOdiA-PC sensing plausibly lies within the nasal cavity of the animal.Animals have highly developed chemosensory systems that enable efficient detection of diverse soluble or volatile molecules. Detection of exogenous molecules by taste bud cells and/or olfactory receptor cells transmits signals to the brain and consequently induces various behavioural responses (e.g., appetitive or aversive response to foods) (21, 25). To better understand the mechanisms underlying chemosensory perception, much effort has gone into identifying sensory proteins in the oral and nasal cavities (4, 5). CD36 is a broadly expressed transmembrane protein associated with the recognition of multiple molecules (e.g., amphipathic lipids) (15,19). For instance, in macrophages, CD36 contributes to the clearance of oxidised forms of low-density lipoprotein from the blood by recognising distinct phospholipid species on the surface of the particles (6,20). Furthermore, CD36 expressed by enterocytes is believed to participate in not only recognition and absorption of long-chain fatty acids but also in formation of chylomicrons (18). In addition to its well-characterized functions, CD36 has been postulated to play an important role in the chemosensory detection of longchain fatty acids in the oral cavity, leading to an appetitive response to the lipid species in rodents. Several lines of evidence support this finding: CD36 is localised to the apical surface of taste bud cells in

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Section: Methodsmentioning

confidence: 99%

A role of CD36 in the perception of an oxidised phospholipid species in mice

et al. 2015

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“…FFA4 is also expressed on murine C2C12 and rat L6 myoclasts, where it was shown to modulate DHA-mediated GLUT4 translocation and glucose uptake via a mechanism dependent on Ca 2+ /CaMKK/AMPK signaling [61]. These data are in contrast to those that show that FFA4 plays no role in fatty acid uptake and oxidation in muscle during endurance exercise [62]. Taken together, these results demonstrate that FFA4 influences inflammation of muscle as well as uptake and metabolism of glucose, but not of fatty acids.…”

Section: Ffa4 Expression and Tissue-specific Physiological Functionsmentioning

confidence: 99%

Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders

Moniri

2016

Biochemical Pharmacology

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Over the last decade, a subfamily of G protein-coupled receptors that are agonized by endogenous and dietary free-fatty acids (FFA) has been discovered. These free-fatty acid receptors include FFA2 and FFA3, which are agonized by short-chained FFA, as well as FFA1 and FFA4, which are agonized by medium-to-long chained FFA. Ligands for FFA1 and FFA4 comprise the family of long chain polyunsaturated omega-3 fatty acids including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting that many of the long-known beneficial effects of these fats may be receptor mediated. In this regard, FFA4 has gathered considerable interest due to its role in ameliorating inflammation, promoting insulin sensitization, and regulating energy metabolism in response to FFA ligands. The goal of this review is to summarize the body of evidence in regard to FFA4 signal transduction, its mechanisms of regulation, and its functional role in a variety of tissues. In addition, recent endeavors toward discovery of small molecules that modulate FFA4 activity are also presented.

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“…; Fujitani et al. ). Exercise training in these mice upregulated mitochondrial proteins (McFarlan et al.…”

Section: Introductionmentioning

confidence: 98%

CD36 is essential for endurance improvement, changes in whole-body metabolism, and efficient PPAR-related transcriptional responses in the muscle with exercise training

et al. 2017

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Although circulating fatty acids are utilized as energy substrates, they also function as ligands to the peroxisome‐proliferator activated receptors (PPARs), a family of fatty acid sensing transcription factors. Exercise training leads to various adaptations in the muscle such as elevation of glycogen content, mitochondrial number as well as upregulation of fatty acid uptake and utilization through downstream transcriptional adaptations. In line with this, CD36 has been shown to be critical in controlling fatty acid uptake and consequently, fatty acid oxidation. We show that exercise training could not ameliorate impaired endurance performance in CD36 KO mice despite intact adaptations in muscle glycogen storage and mitochondrial function. Changes in whole‐body metabolism at rest and during exercise were also suppressed in these animals. Furthermore, there was inefficient upregulation of PPAR and PPAR‐related exercise‐responsive genes with chronic training in CD36 KO mice despite normal upregulation of Pgc1a and mitochondrial genes. Our findings supplement previous observations and emphasize the importance of CD36 in endurance performance, energy production and efficient downstream transcriptional regulation by PPARs.

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CD36, but not GPR120, is required for efficient fatty acid utilization during endurance exercise

Cited by 14 publications

References 34 publications

<b>A role of CD36 in the perception of an oxidised phospholipid species in </b><b>mice </b>

<b>A role of CD36 in the perception of an oxidised phospholipid species in </b><b>mice </b>

Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders

CD36 is essential for endurance improvement, changes in whole-body metabolism, and efficient PPAR-related transcriptional responses in the muscle with exercise training

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