FFA4/GPR120: Pharmacology and Therapeutic Opportunities

Milligan, Graeme; Álvarez-Curto, Elisa; Hudson, Brian D.; Prihandoko, Rudi; Tobin, Andrew B.

doi:10.1016/j.tips.2017.06.006

Cited by 83 publications

(60 citation statements)

References 79 publications

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“…When hexadecanoic acid (a saturated 16-carbon fatty acid) was added to the potato chip lowest in fat, it was rated as fattier but was less liked than a potato chip with a comparable amount of fat but without the added fatty acid. Thus, presumably, taking a broader view and generalizing, this result suggests that increasing “fattiness” by adding fatty acids to foods would not make them better liked, and raises the possibility that recently discovered antagonists to the fatty acid receptors (Milligan et al 2017) might improve fat flavor. These data support the hypothesis that there are at least two sensory inputs for fat perception, a chemical cue and presumably a textural cue, with the texture conveying perhaps the pleasant aspects of fattiness.…”

Section: Discussionmentioning

confidence: 99%

Studies of human twins reveal genetic variation that affects dietary fat perception

Lin

Colquitt

Wise

et al. 2020

Preprint

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To learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1×10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

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Section: Discussionmentioning

confidence: 99%

Studies of human twins reveal genetic variation that affects dietary fat perception

Lin

Colquitt

Wise

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Future studies are needed to clarify the role of GPR120 in the gonadotropes after HFD feeding. GPR120 is reported to engage multiple signal pathways through Gq/11, Gi family, or β-arrestin [41]. It is well known that Gi proteins decrease activity of cAMP-dependent protein kinases, such as protein kinase A (PKA).…”

Section: Discussionmentioning

confidence: 99%

Short-term but not long-term high-fat diet induces an increase in gene expression of gonadotropic hormones and GPR120 in the male mouse pituitary gland

Deura

Moriyama

2020

Journal of Reproduction and Development

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High-fat diet (HFD) is associated with the regulation of reproductive functions. This study aimed to investigate the effects of short-term HFD on the mRNA expression levels of follicle-stimulating hormone β subunit (FSHβ), luteinizing hormone β subunit (LHβ), gonadotropin-releasing hormone receptor, and long-chain fatty acid receptor, GPR120, in the matured male mouse pituitary gland. Adult male mice were fed either control chow or HFD for 1, 2, 5, 10, 30 and 150 days. Fshb and Gpr120 mRNA expression levels in the pituitary glands were significantly increased during 2 to 30 days of HFD feeding. Gnrh-r mRNA in the 30 days HFD fed group and body weight in the 30 and 150 days HFD fed groups were higher than control. However, there were no significant differences in plasma non-esterified fatty acids or glucose levels during the 150 days of HFD feeding. These results suggest that male mice feeding a short-term HFD induces FSHβ synthesis and GPR120 expression in their pituitary gonadotropes.

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“…Furthermore, it has been established that the ERK1/2 pathway is located downstream of GPR120 to regulate several physiological functions such as GLP-1 secretion [2] and cytosolic phospholipase A2 activation [32]. In addition, GPR120 is a Gq/11, Gi family member, or β-arrestin coupled GPCR [33]. Among these three intermediate molecules, the Gi proteins have been shown to decrease the activity of protein kinase A (PKA) by inhibiting adenylyl cyclase activity [34].…”

Section: Discussionmentioning

confidence: 99%

<i>Gpr120</i> mRNA expression in gonadotropes in the mouse pituitary gland is regulated by free fatty acids

Deura

Kimura

et al. 2020

Journal of Reproduction and Development

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GPR120 is a long-chain fatty acid (LCFA) receptor that is specifically expressed in gonadotropes in the anterior pituitary gland in mice. The aim of this study was to investigate whether GPR120 is activated by free fatty acids in the pituitary of mice and mouse immortalized gonadotrope LβT2 cells. First, the effects of palmitate on GPR120, gonadotropic hormone b-subunits, and GnRH-receptor expression in gonadotropes were investigated in vitro. We observed palmitate-induced an increase in Gpr120 mRNA expression and a decrease in Fshb expression in LβT2 cells. Furthermore, palmitate exposure caused the phosphorylation of ERK1/2 in LβT2 cells, but no significant changes were observed in the expression levels of Lhb and Gnrh-r mRNA and number of GPR120 immunoreactive cells. Next, diurnal variation in Gpr120 mRNA expression in the male mouse pituitary gland was investigated using ad libitum and night-time restricted feeding (active phase from 1900 to 0700 h) treatments. In ad libitum feeding group mice, Gpr120 mRNA expression at 1700 h was transiently higher than that measured at other times, and the peak blood non-esterified fatty acid (NEFA) levels were observed from 1300 to 1500 h. These results were not observed in night-time-restricted feeding group mice. These results suggest that GPR120 is activated by LCFAs to regulate FSH synthesis in the mouse gonadotropes.

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FFA4/GPR120: Pharmacology and Therapeutic Opportunities

Cited by 83 publications

References 79 publications

Studies of human twins reveal genetic variation that affects dietary fat perception

Studies of human twins reveal genetic variation that affects dietary fat perception

Short-term but not long-term high-fat diet induces an increase in gene expression of gonadotropic hormones and GPR120 in the male mouse pituitary gland

<i>Gpr120</i> mRNA expression in gonadotropes in the mouse pituitary gland is regulated by free fatty acids

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