Whole Milk Increases Intestinal ANGPTL4 Expression and Excretion of Fatty Acids through Feces and Urine

Abstract

The angiopoietin-like 4 (ANGPLT4) protein is involved in lipid metabolism and is known to inhibit lipoprotein lipase in the bloodstream. We investigated the effect of milk on intestinal ANGPTL4 and the metabolic profile of growing pigs and the effect of free fatty acids (FFAs) on ANGPTL4 in ex vivo and in vitro assays. Feeding pigs whole milk increased intestinal ANGPTL4 mRNA and increased fecal excretion of long-chain FFA compared to the control group fed soybean oil (n = 9). Furthermore, FFAs (C4-C8) induced ANGPTL4 gene expression in porcine intestinal tissue mounted in Ussing chambers and ANGPTL4 protein secretion to both the apical and basolateral sides of intestinal Caco-2 cells on permeable membranes. Altogether, these results support an ANGPTL4-induced secretion of fecal FFAs. Urinary levels of FFAs (C4-C12), 3-hydroxyadipic acid, and suberic acid were also increased by milk consumption, indicating higher energy expenditure compared to the control group.

Consumption of Whey in Combination with Dairy Medium‐Chain Fatty Acids (MCFAs) may Reduce Lipid Storage due to Urinary Loss of Tricarboxylic Acid Cycle Intermediates and Increased Rates of MCFAs Oxidation

“…These observations might provide a potential explanation of the clinical observation on increased lean body mass in the two diet groups consuming high levels of MCFAs . Furthermore, levels of the urinary dicarboxylic fatty acids, 3‐hydroxyadipic acid, and suberic acid, were increased after the consumption of milk‐based diet in an animal (pigs) study as compared to before the intervention and also to the control diet at the end of the intervention as shown in Nielsen and Amer et al., which also correlates with our findings. Adipic acid concentration was higher in CH urine as compared to WH at the end of the intervention, suggesting a synergetic effect of caseins on the ω‐oxidation of MCFAs.…”

“…Samples were treated according to Nielsen and Amer et al . Please consult Supporting Information for a detailed description of sample preparations.…”

“…The samples were injected in a 1:40 split mode into an Agilent Technologies 7890B GC system coupled to an Agilent Technologies 7200 Accurate‐Mass QTOF/MS (Agilent Technologies, Germany) according to Nielsen and Amer et al . Detailed analysis parameters are shown in Supplementary Materials.…”

The Effect of Partly Replacing Vegetable Fat with Bovine Milk Fat in Infant Formula on Postprandial Lipid and Energy Metabolism: A Proof‐of‐principle Study in Healthy Young Male Adults

“…Immediately after consumption, the relative C12:0 and C14:0 content in CMRF seemed lower than in the test drinks. This may related to higher water solubility of FAs <C14, [42] facilitating direct uptake into the portal vein. [43] This study thus indicates that C14:0, like C12:0, may partly be directly absorbed without inclusion in chylomicrons.…”

Digestion of human milk fat in healthy infants

“…In comparison to germ-free mice, mice colonized with Bacteroides thetaiotaomicron showed elevated gene expression of PLRP-2, colipase, liver-type fatty acidbinding protein, and apolipoprotein A-IV in the ileum [155]. Intestinal gene expression of angiopoietin-like protein 4 (Angptl4) was 2.5-fold higher in pigs fed a milk-based diet than a control diet [156]. Angptl4 may be part of a negative feedback mechanism to protect against lipotoxicity [157], as its activity reduces the activity of PTL and increases fat excretion in stool [158].…”