Revisiting the metabolism and physiological functions of caprylic acid (C8:0) with special focus on ghrelin octanoylation

Lemarié, Fanny; Beauchamp, Erwan; Legrand, Philippe; Rioux, Vincent

doi:10.1016/j.biochi.2015.08.002

Cited by 69 publications

(37 citation statements)

References 107 publications

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“…OA, also known as caprylic acid, has antibacterial activity 14 . Moreover, OA was recently reported to act as an HDAC inhibitor like VPA, albeit less effective 15 .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates

Novohradský

Zanellato

Marzano

et al. 2017

Sci Rep

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We present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)2Cl2(OA)2] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV)diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV)diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity. The potency of Pt(IV)diOA is a consequence of several factors including enhanced cellular accumulation correlating with enhanced DNA platination and cytotoxicity. Pt(IV)diOA induces DNA hypermethylation and reduces mitochondrial membrane potential in cancer cells at levels markedly lower than the IC50 value of free OA suggesting the synergistic action of platinum and OA moieties. Collectively, the remarkable antitumor effects of Pt(IV)diOA are a consequence of the enhanced cellular uptake which makes it possible to simultaneously accumulate high levels of both cisplatin and OA in cells. The simultaneous dual action of cisplatin and OA by different mechanisms in tumor cells may result in a markedly enhanced and unique antitumor effects of Pt(IV) prodrugs.

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“…OA, also known as caprylic acid, has antibacterial activity 14 . Moreover, OA was recently reported to act as an HDAC inhibitor like VPA, albeit less effective 15 .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates

Novohradský

Zanellato

Marzano

et al. 2017

Sci Rep

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“…Underlying these immediate effects of MCT may be their different route of absorption in contrast to long-chain (LC) FA, i.e., >C12, medium-chain fatty acids (MCFA) (C8-12) are mainly absorbed via the portal vein, and as MCFA readily cross the mitochondrial membrane (mainly carnitine-independently), they are rapidly oxidised in liver and muscle to supply energy and body heat [14,15]. This is why high dietary MCT levels spare LCFA from oxidation, thus promoting LCFA plasma levels and their storage in adipose cells.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, MCFA are almost completely oxidized and minimally stored in fat tissue. Because of their rapid and complete oxidation, MCFA are ketogenic and have (hence) a high satiating effect [15]. …”

Section: Introductionmentioning

confidence: 99%

An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

et al. 2017

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Medium-chain fatty acids (MCFA) are a directly and readily absorbed source of energy. Exposure early-in-life to increased MCFA levels might affect development and impact (lipid) metabolism later in life. We tested whether an increased MCFA intake early-in-life positively affects adult body composition and metabolic status when challenged by a western-style diet (WSD). Male offspring of C57Bl/6j mice and Wistar rats were fed a control diet (CTRL; 10 w% fat, 14% MCFA) or a medium-chain triglycerides (MCT) diet with 20% MCFA until postnatal (PN) day 42, whereupon animals were fed a WSD (10 w% fat) until PN day 98. Body composition was monitored by Dual Energy X-ray Absorptiometry (DEXA). In rats, glucose homeostasis was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT); in mice, the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. At autopsy on PN day 98, plasma lipid profiles, glucose, insulin, and adipokines were measured; organs and fat pads were collected and the adipocyte size distribution was analysed. Milk analysis in mice showed that the maternal MCT diet was not translated into milk, and pups were thus only exposed to high MCT levels from early weaning onward: PN day 16 until 42. Mice exposed to MCT showed 28% less fat accumulation vs. CTRL during WSD. The average adipocyte cell size, fasting plasma triglycerides (TG), and leptin levels were reduced in MCT mice. In rats, no effects were found on the adult body composition, but the adipocyte cell size distribution shifted towards smaller adipocytes. Particularly mice showed positive effects on glucose homeostasis and insulin sensitivity. Increased MCFA intake early-in-life protected against the detrimental effects of an obesogenic diet in adulthood.

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“…Three pathways control ghrelinstimulated GH release: direct effect on pituitary cells, direct effect from the hypothalamus and indirect effect by vagus nerve pathway signaling which increases noradrenaline in the arcuate nucleus of the hypothalamus leading a central control of feeding behavior. This is an indirect pathway control because of the peptide do not pass the blood-brain barrier in the high levels 46,53 . Date et al 54 have demonstrated that vagotomy abolish fast-induced elevation of ghrelin plasma levels.…”

Section: Ghrelinmentioning

confidence: 99%