DHA attenuates postprandial hyperlipidemia via activating PPARα in intestinal epithelial cells

Kimura, Ryoji; Takahashi, Nobuyuki; Lin, Shuo; Goto, Tsuyoshi; Murota, Kazuo; Nakata, Rieko; Inoue, H.; Kawada, Teruo

doi:10.1194/jlr.m034942

Cited by 43 publications

(39 citation statements)

References 49 publications

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“…Fatty acid oxidation (FAO) takes place mainly within mitochondria and has the potential to reduce the availability of fatty acids for TAG synthesis and incorporation into CMs and CLDs [43–45]. Therefore, we determined mRNA levels of genes involved in FAO and the ratio of mitochondrial DNA to genomic DNA (indicator of mitochondrial content) in enterocytes of WT, Dgat1 Int , Dgat2 Int , and Dgat1 −/− mice 2 hours after a 200 μl oral olive oil gavage.…”

Section: Resultsmentioning

confidence: 99%

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

Hung

Carreiro

Buhman

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Enterocytes, the absorptive cells of the small intestine, mediate efficient absorption of dietary fat (triacylglycerol, TAG). The digestive products of dietary fat are taken up by enterocytes, re-esterified into TAG, and packaged on chylomicrons (CMs) for secretion into blood or temporarily stored within cytoplasmic lipid droplets (CLDs). Altered enterocyte TAG distribution impacts susceptibility to high fat diet associated diseases, but molecular mechanisms directing TAG toward these fates are unclear. Two enzymes, acyl CoA: diacylglycerol acyltransferase 1 (Dgat1) and Dgat2, catalyze the final, committed step of TAG synthesis within enterocytes. Mice with intestine-specific overexpression of Dgat1 (Dgat1Int) or Dgat2 (Dgat2Int), or lack of Dgat1 (Dgat1−/−), were previously found to have altered intestinal TAG secretion and storage. We hypothesized that varying intestinal Dgat1 and Dgat2 levels alters TAG distribution in subcellular pools for CM synthesis as well as the morphology and proteome of CLDs. To test this we used ultrastructural and proteomic methods to investigate intracellular TAG distribution and CLD-associated proteins in enterocytes from Dgat1Int, Dgat2Int, and Dgat1−/− mice 2 hours after a 200 μl oral olive oil gavage. We found that varying levels of intestinal Dgat1 and Dgat2 altered TAG pools involved in CM assembly and secretion, the number or size of CLDs present in enterocytes, and the enterocyte CLD proteome. Overall, these results support a model where Dgat1 and Dgat2 function coordinately to regulate the process of dietary fat absorption by preferentially synthesizing TAG for incorporation into distinct subcellular TAG pools in enterocytes.

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Section: Resultsmentioning

confidence: 99%

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

Hung

Carreiro

Buhman

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…For example, dietary supplementation of polyunsaturated FAs (docosahexanoic acid, eicosapentanoic acid, and α-linolenic acid) [182-184] and 1,3-DAG [185-187] were found to induce intestinal FAO and contribute to hypotriglyceridemic and anti-obesity effects. The induction of intestinal FAO by polyunsaturated FAs occurs through the activation of transcription factors (PPARα) or cellular molecules (AMP-activated protein kinase [188, 189]) involved in lipid catabolism.…”

Section: Cytoplasmic Lipid Droplet (Cld) Catabolism In Enterocytesmentioning

confidence: 99%

“…PPARα has a variety of natural ligands (unsaturated FAs, leukotriene B4, docosahexaenoic acid, and eicosapentaenoic acid) and synthetic ligands (fenofibrate, clofibrate, and gemfibrozil) [216]. Both natural and synthetic PPARα agonists reduce the postprandial triglyceridemic response, a risk factor for cardiovascular disease [182, 191]. PPARα mRNA is present along the entire length of the small intestine with highest levels in duodenum and jejunum, as well as higher levels in villus tips than in crypts [217, 218].…”

Section: Regulation Of Cytoplasmic Lipid Droplet (Cld) Metabolism mentioning

confidence: 99%

“…PPARα mRNA is present along the entire length of the small intestine with highest levels in duodenum and jejunum, as well as higher levels in villus tips than in crypts [217, 218]. Additionally, intestinal PPARα levels increase in response to dietary fat consumption [4, 182, 183], synthetic agonists (fenofibrate and benzafibrate) [191, 219] and endurance exercise training [142]. …”

Section: Regulation Of Cytoplasmic Lipid Droplet (Cld) Metabolism mentioning

confidence: 99%

“…Mice fed docosahexaenoic acid enriched diets have decreased intestinal TAG storage and TAG secretion compared to mice fed an isocaloric, non-polyunsaturated FA control diet [182]. In addition, high-fat fed mice given fenofibrate also exhibit decreased intestinal TAG storage in CLDs and decreased TAG secretion [191].…”

Section: Regulation Of Cytoplasmic Lipid Droplet (Cld) Metabolism mentioning

confidence: 99%

See 2 more Smart Citations

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes

D’Aquila

Hung

Carreiro

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

115

122

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Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of cytoplasmic lipid droplets within this process.

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Herring and chicken/pork meals lead to differences in plasma levels of TCA intermediates and arginine metabolites in overweight and obese men and women

Vincent

Savolainen

Sen

et al. 2016

Molecular Nutrition Food Res

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DHA attenuates postprandial hyperlipidemia via activating PPARα in intestinal epithelial cells

Cited by 43 publications

References 49 publications

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes

Herring and chicken/pork meals lead to differences in plasma levels of TCA intermediates and arginine metabolites in overweight and obese men and women

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