Recent concepts of intestinal fat absorption

Obesity is becoming one of the greatest threats to global health in the 21st century and therefore the development of novel antiobesity drugs is one of the top priorities of global drug research. An important treatment strategy includes the reduction of intestinal fat absorption through the inhibition of pancreatic lipase (PL). Natural products provide a vast pool of PL inhibitors with novel scaffolds that can possibly be developed into clinical products. Computational drug design methods have become increasingly invaluable in the drug discovery process. In recent years, the discovery of new antiobesity PL inhibitors has been facilitated by the application of computational methods. This review highlights some computer-aided drug design techniques utilized in the discovery of natural PL inhibitors.

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AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity

Cell Metabolism ◽

10.1016/j.cmet.2018.02.021 ◽

2018 ◽

Vol 27 (4) ◽

pp. 843-853.e6 ◽

Cited By ~ 8

Author(s):

Hui Luo ◽

Ming Jiang ◽

Guili Lian ◽

Qing Liu ◽

Meng Shi ◽

...

Keyword(s):

Fat Absorption ◽

Intestinal Fat Absorption ◽

Fat Synthesis

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ON the Mechanism of the Intestinal Fat Absorption: Metabolism of Lipids 6

Acta Physiologica Scandinavica ◽

10.1111/j.1748-1716.1952.tb00882.x ◽

1952 ◽

Vol 25 (4) ◽

pp. 291-314 ◽

Cited By ~ 36

Author(s):

BENGT BORGSTRÖM

Keyword(s):

Fat Absorption ◽

Intestinal Fat Absorption

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On the Mechanism of the Intestinal Fat Absorption V.: The Effect of Bile Diversion on Fat Absorption in the Rat.1

Acta Physiologica Scandinavica ◽

10.1111/j.1748-1716.1953.tb00981.x ◽

1953 ◽

Vol 28 (2-3) ◽

pp. 279-286 ◽

Cited By ~ 32

Author(s):

BENGT BORGSTROM.

Keyword(s):

Fat Absorption ◽

Intestinal Fat Absorption

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Short-chain Fatty Acids, 4-phenylbutyric Acid and R-α-lipoic Acid, Downregulate mTORC1-dependent Intestinal Fat Absorption (P08-115-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-115-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Regis Moreau ◽

Bo He

Keyword(s):

Lipoic Acid ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Fat Absorption ◽

Genetic Ablation ◽

Funding Sources ◽

Knowing That ◽

Intestinal Fat Absorption ◽

Fat Diets ◽

Phenylbutyric Acid

Abstract Objectives Knowing that (i) high-fat diets upregulate inflammatory biomarkers in the small intestine and activate the mechanistic target of rapamycin complex 1 (mTORC1, a conserved protein kinase) and (ii) mTORC1 drives hepatic VLDL secretion, we investigated the role of intestinal mTORC1 in fat absorption and the lipid-regulating properties of 4-phenylbutyric acid (PBA) and R-α-lipoic acid (LA) in relation to mTORC1. Methods Lentivirus shRNA-based gene editing was utilized to create three stable Caco-2 cell lines that exhibit low, normal or high mTORC1 activity. Fat absorption was investigated in differentiated stable Caco-2 cells grown with oleate/albumin in Transwell permeable inserts. Results Genetic ablation of mTORC1 revealed that mTORC1 is required for the production and secretion of apoB-containing chylomicrons in Caco-2 cells. Rapamycin, an inhibitor of mTORC1, confirmed this finding as it lowered the secretion of apoB48 (−75%) and apoB100 (−47%) (P < 0.05). mTORC1 deletion was accompanied by the downregulation of APOB (−87%), MTTP (−94%), FASN (−76%), DGAT1 (−77%) and DGAT2 (−81%) genes (all P < 0.05); lower cellular abundance of apoB100 (−89%), MTTP (−63%) and FASN (−80%) (all P < 0.05); and lower media abundance of apoB48 (−66%), apoB100 (−51%) and triacylglycerols (−69%) (all P < 0.05). In Caco-2 cells harboring high mTORC1 activity, PBA or LA decreased the amounts of secreted apoB48 (−58% or −22%, respectively), apoB100 (−54% or −43%), and triacylglycerols (−46% or −38%), and the gene expression of APOB (−48% or −33%), MTTP (−54% or −31%), SREBF1 (−39% or −37%), FASN (−84% or −38%), and DGAT2 (−76% or −47%) (all P < 0.05). Conclusions A functional intestinal mTORC1 is indispensable for chylomicron production. Intake of short-chain fatty acid, PBA or LA, may be useful to prevent chylomicron overproduction-associated hypertriglyceridemia and postprandial inflammation. Funding Sources USDA Hatch Act, USDA-AFRI.

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