Metabolic adaptations to dietary fat malabsorption in chylomicron-deficient mice

• Published in: Biochemical journal Vol. 343; no. 2; pp. 473 - 478
• Main Authors: Jung, H.R, Turner, S.M, Neese, R.A, Young, S.G, Hellerstein, M.K
• Format: Journal Article
• Language: English
• Published: England 15-10-1999
• Subjects: Adipose Tissue - metabolism; Aging; Animals; Apolipoproteins B - genetics; Apolipoproteins B - metabolism; Apolipoproteins B - secretion; Body Composition; Cholesterol - biosynthesis; Cholesterol - blood; Chylomicrons - genetics; Chylomicrons - physiology; dietary fat; Dietary Fats - metabolism; Esters - metabolism; fat absorption; fatty acid turnover; Fatty Acids - analysis; Fatty Acids - blood; Fatty Acids - metabolism; Fatty Acids, Nonesterified - blood; Fatty Acids, Nonesterified - metabolism; Humans; lipogenesis; Liver - metabolism; Liver - secretion; Malabsorption Syndromes - genetics; Malabsorption Syndromes - metabolism; Matched-Pair Analysis; Mice; Mice, Transgenic; Organ Specificity; Triglycerides - analysis; Triglycerides - blood; Triglycerides - metabolism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/0264-6021:3430473

A mouse model of chylomicron deficiency was recently developed; these mice express a human apolipoprotein (apo) B transgene in the liver but do not synthesize any apoB in the intestine. Despite severe intestinal fat malabsorption, the mice maintain normal concentrations of plasma lipids and liver-derived apoB 100-containing lipoproteins. We investigated the metabolic mechanisms by which plasma lipid levels are kept normal. De novo lipogenesis (DNL) and cholesterogenesis were measured by mass isotopomer distribution analysis (MIDA). Plasma non-esterified fatty acid (NEFA) fluxes and hepatic re-esterification of labelled plasma NEFA were also measured. Hepatic and plasma triacylglycerol (TG) concentrations and plasma NEFA fluxes were not different between chylomicron-deficient mice and controls. The contribution from DNL to the hepatic TG pool was only modestly higher in chylomicron-deficient mice [12+/-2.1% (n=7) compared with 3.7+/-1.0% (n=9); means+/-S.E.M.], whereas cholesterogenesis was markedly elevated. The fractional contribution from plasma NEFA to hepatic TG was greatly elevated in the chylomicron-deficient animals (62% compared with 23%). Accordingly, 73% of hepatic TG was neither from DNL nor from plasma NEFA in controls, presumably reflecting prior contribution from chylomicron remnants, compared with only 26% in the chylomicron-deficient group. The long-term contribution from DNL to adipose fat stores reached approximately the same steady-state values (approximately 30%) in the two groups. Body fat accumulation was much lower in chylomicron-deficient animals; thus, whole-body absolute DNL was significantly lower. We conclude that plasma and hepatic TG pools and hepatic secretion of apoB-containing particles are maintained at normal levels in chylomicron-deficient mice, not by de novo fatty acid synthesis, but by more avid re-esterification of plasma NEFA, replacing the normally predominant contribution from chylomicrons, and that some dietary fat can be absorbed by apoB-independent mechanisms.