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Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice.

ABSTRACT: We evaluated the biological basis of reduced fat gain by oleoylethanolamide (OEA) in high-fat-fed mice and sought to determine how degradation of OEA affected its efficiency by comparing its effects to those of KDS-5104, a nonhydrolyzable lipid OEA analog. Mice were given OEA or KDS-5104 by the oral route (100 mg/kg body weight). Sixty-eight variables per mouse, describing six biological processes (lipid transport, lipogenesis, energy intake, energy expenditure, endocannabinoid signaling, and glucose metabolism), spanning gene expression of biochemical and physiological parameters were examined to determine the primary target whereby OEA reduces fat gain. Although KDS-5104 but not OEA was resistant to fatty acid amide hydrolase hydrolysis, OEA was degraded by an unidentified hydrolysis system in the liver. Nevertheless, both compounds equally decreased body fat pads after 5 weeks (20%; P < 0.05). The six biological functions constructed from the 68 initial variables predicted up to 58% of adipose fat variations. Lipid transport appeared central to the explanation for body fat deposition (16%; P < 0.0001), in which decreased expression of the FAT/CD36 gene was the component most related to adipose depots. Lipid transport appears to be a determinant player in the OEA fat-lowering response, with adipose tissue FAT/CD36 expression being the most relevant bioindicator of OEA action.

SUBMITTER: Thabuis C

PROVIDER: S-EPMC3111743 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice.

Thabuis Clémentine C Destaillats Frédéric F Lambert Didier M DM Muccioli Giulio G GG Maillot Matthieu M Harach Touafiq T Tissot-Favre Delphine D Martin Jean-Charles JC

Journal of lipid research 20110424 7

We evaluated the biological basis of reduced fat gain by oleoylethanolamide (OEA) in high-fat-fed mice and sought to determine how degradation of OEA affected its efficiency by comparing its effects to those of KDS-5104, a nonhydrolyzable lipid OEA analog. Mice were given OEA or KDS-5104 by the oral route (100 mg/kg body weight). Sixty-eight variables per mouse, describing six biological processes (lipid transport, lipogenesis, energy intake, energy expenditure, endocannabinoid signaling, and gl ...[more]

PMID: 21515921

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Project description:BackgroundCombined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated.MethodsFemale mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring.ResultsHFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator-activated receptor-γ co-activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring.ConclusionsLeucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

Project description:Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups (n=6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively). HFD Y340 and HFD Y680 rats exhibited marked attenuation of weight gain, a decrease in visceral fat pad weight, a restoration of the serum lipid profile and atherogenic index in a dose-dependent manner, being the higher dose more effective (p < 0.05). In addition, we found that HFD Y680 rats showed lower glucose and insulin levels, improved glucose tolerance, and insulin sensitivity (p < 0.5). A downregulation of several adipocyte specific-transcription factors, including peroxisome proliferator-activated receptor gamma2 (PPAR-γ2), CCAAT/enhancer binding protein a (C/EBP-a) and activating protein (aP2) mRNA levels, was determined in the visceral adipose tissue of HFD Y680 rats (p < 0.05). An improvement of adipokine profile in HFD Y680 rats and decreased serum proinflammatory cytokine levels (p < 0.05) were determined by ELISA. Decreased macrophage infiltration and F4/80 and MCP-1 expression in the visceral adipose tissue of HFD Y680 rats (p < 0.5), together with a higher pAkt/Akt expression (p < 0.05) were also observed by immunofluorescence and immunoblotting. A significant increase in glucagon (Gcg) and PYY mRNA levels in distal ileum of HFD Y680 rats (p < 0.05) were also detected. In the second approach, we determined that yacon supplementation potentiates the effects of the HFD reversion to a standard diet. In conclusion, yacon showed antiobesity properties by inhibiting adipogenesis and improving the visceral adipose tissue function.

Dataset Information

Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice.

Publications

Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice.

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