Free Fatty Acid Receptors and Drug Discovery

Hirasawa, Akira; Hara, Takafumi; Katsuma, Susumu; Adachi, Tomohiko; Tsujimoto, Gozoh

doi:10.1248/bpb.31.1847

Cited by 140 publications

(96 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently, the G-protein-coupled receptor (GPCR) deorphanizing strategy has successfully identified multiple receptors for free fatty acids (FFAs). 38) Interestingly, among these receptors, the G-protein receptor (GPR) 40 39) and GPR120 are activated by long-chain FFAs such as EPA and DHA. 40) GPR40, which is preferentially expressed in pancreatic bcells, mediates insulin secretion, 41) and GPR120, which is 37) abundantly expressed in the intestine, promotes insulin secretion 42) and the secretion of glucagon-like peptide-1 43) and cholecystokinin.…”

Section: N-3 Pufas and Painmentioning

confidence: 99%

Unsaturated Fatty Acids and Pain

Tokuyama

Nakamoto

2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. Recently, the functional relationship between polyunsaturated fatty acids and pain has been the focus of many studies. Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy. In addition, levels of n-6 series polyunsaturated fatty acids are high in patients with chronic pain. These results indicate that polyunsaturated fatty acids play a vital role in pain regulation. In this review, we summarize a number of basic and clinical studies on polyunsaturated fatty acids and their association with pain.

show abstract

Section: N-3 Pufas and Painmentioning

confidence: 99%

Unsaturated Fatty Acids and Pain

Tokuyama

Nakamoto

2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…медицинской химии ЗАО «Исследовательский институт химического разнообразия», Химки, Россия жирные кислоты и их производные, введение кото-рых приводит к повышению глюкозозависимой се-креции инкретинов, инсулина, снижению массы тела и ряду плейотропных эффектов. Создание син-тетических агонистов к данным рецепторам счита-ется перспективным путем разработки средств регу-ляции углеводного обмена [3][4][5]. Одним из наибо-лее перспективных рецепторов этой группы был признан GPR119 [6,7].…”

Section: сведения об авторахunclassified

“…Во 2-5-й группах средний исходный уровень глюкозы в крови (12,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)6) различался не более чем на 7-8%.…”

Section: материал и методыunclassified

“…ZB-16 является высокоселективным агонистом рецептора GPR119, который был валидирован в ка-честве биомишени для создания противодиабетиче- ских средств [4]. Гипогликемическое действие ZB-16, очевидно, связано со способностью этого соеди-нения стимулировать секрецию кишечных гормо-нов (ГПП-1 и ГИП) и инсулина.…”

Section: результаты и обсуждениеunclassified

See 1 more Smart Citation

Comparing hypoglycemic activity of novel GPR119 agonist and DPP-4 inhibitor sitagliptin

Tyurenkov

Николаевич²,

Куркин

et al. 2016

Probl Endokrinol (Mosk)

View full text Add to dashboard Cite

1 ГБОУ ВПО «Волгоградский государственный медицинский университет», Волгоград, Россия; 2 ЗАО «Исследовательский институт химического разнообразия», Химки, Московская область, Россия В регуляции секреции эндогенных инкретинов участвует ряд рецепторов энтероэндокринных клеток; среди таких рецеп-торов наиболее перспективным был признан GPR119. При его активации повышается секреция инкретинов и возрастает глюкозозависимая секреция инсулина, что важно для эффективного контроля постпрандиальной гликемии и снижения риска гипогликемий. Цель исследования -сравнение гипогликемической активности ингибитора ДПП-4 (ситаглиптина) и нового агониста GPR119 (соединения ZB-16) у животных с экспериментальной формой сахарного диабета 2-го типа (СД2).

show abstract

“…Free fatty acids have been shown to inhibit serum-starved apoptosis in a murine cell model via the G-coupled protein receptor, GPR120 (19). In these experiments, both saturated and unsaturated free fatty acid-enhanced PPARα in the attenuation of apoptosis Articles cell survival, but linolenic acid, palmitoleic acid, and docosahexaenoic acid (DHA) had the most potent effects on cell survival (20). In addition, GPR120 has recently been shown to be a receptor or sensor for ω3PUFA, mediating regulation of inflammation, and inhibiting both toll-like receptor 2/3/4 and tumor necrosis factor-α cascades (21).…”

mentioning

confidence: 99%

Role of PPARα in the attenuation of bile acid-induced apoptosis by omega-3 long-chain polyunsaturated fatty acids in cultured hepatocytes

et al. 2016

View full text Add to dashboard Cite

Background: Omega-3 long-chain polyunsaturated fatty acids (ω3PUFA) have been shown to be antiinflammatory in the attenuation of hepatocellular injury. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that inhibits the activation of nuclear factor κB, thereby repressing inflammation, and ωPUFA are PPARα ligands. The purpose of this study was to determine if ω3PUFA attenuate bile acid-induced apoptosis via PPARα. Methods: Human hepatocellular carcinoma (HepG2) cells were treated with chenodeoxycholic acid (CDCA) ± ω3PUFA. Activation of PPARα was evaluated, and expression of PPARα, farnesoid X receptor, liver X receptor alpha (LXRα), and retinoid X receptor mRNA was evaluated by reverse-transcriptase PCR. results: PPARα activation was increased in HepG2 cells treated with ω3PUFA, and decreased in the presence of CDCA when compared with untreated cells. PPARα mRNA was reduced by 67% with CDCA and restored to the level of control with ω3PUFA. LXRα mRNA increased twofold with CDCA treatment and was significantly reduced by ω3PUFA. conclusion: Expression of PPARα, as well as LXRα mRNA levels, was reduced with CDCA treatment and restored with the addition of ω3PUFA. These results suggest that PPARα and LXRα may be mediators by which ω3PUFA attenuate bile acid-induced hepatocellular injury.

show abstract

Free Fatty Acid Receptors and Drug Discovery

Cited by 140 publications

References 41 publications

Unsaturated Fatty Acids and Pain

Unsaturated Fatty Acids and Pain

Comparing hypoglycemic activity of novel GPR119 agonist and DPP-4 inhibitor sitagliptin

Role of PPARα in the attenuation of bile acid-induced apoptosis by omega-3 long-chain polyunsaturated fatty acids in cultured hepatocytes

Contact Info

Product

Resources

About