New Insights into the Regulation of Chylomicron Production

Abstract

Dietary lipids are efficiently absorbed by the small intestine, incorporated into triglyceride-rich lipoproteins (chylomicrons), and transported in the circulation to various tissues. Intestinal lipid absorption and mobilization and chylomicron synthesis and secretion are highly regulated processes. Elevated chylomicron production rate contributes to the dyslipidemia seen in common metabolic disorders such as insulin-resistant states and type 2 diabetes and likely increases the risk for atherosclerosis seen in these conditions. An in-depth understanding of the regulation of chylomicron production may provide leads for the development of drugs that could be of therapeutic utility in the prevention of dyslipidemia and atherosclerosis. Chylomicron secretion is subject to regulation by various factors, including diet, body weight, genetic variants, hormones, nutraceuticals, medications, and emerging interventions such as bariatric surgical procedures. In this review we discuss the regulation of chylomicron production, mechanisms that underlie chylomicron dysregulation, and potential avenues for future research.

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

“…Diminished post-translational apoB-100 degradation in hepatocytes with increased biogenesis, stability, and secretion of nascent VLDL particles has been demonstrated in insulin resistance, resulting in increased production of VLDL by the liver (42). Although there are some differences in the regulation of VLDL and chylomicron particle production, similar mechanisms are also likely to be involved in enhancing chylomicron production in the intestine (43,44). Thus, the production of intestinally derived TRL apoB-48 is also increased in insulin resistance (45), obesity (46), and T2D (47,48), and chylomicron TG secretion is increased in metabolic syndrome (49).…”

“…Recent advances in the understanding of intestinal lipoprotein production offer novel therapeutic approaches in attenuating postprandial lipemia (reviewed in Dash et al [44]). Among those, the incretin-based antidiabetic drugs exenatide (a glucagon-like peptide-1 receptor agonist) and sitagliptin (a dipeptidyl peptidase-4 inhibitor) suppress intestinal lipoprotein production in the short term in humans (119,120).…”

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

“…Lipoproteins present diverse sizes (7-1200 nm of diameter) and can be classified based on their respective density or electrophoretic mobility [47]. The exogenous lipoprotein pathway, which comprises the apoB48-containing lipoproteins, consists in dietary lipid transport from the intestine to energy-demanding tissues such as muscle, adipose tissue and the liver [46,[48][49][50][51][52][53]. The endogenous lipoprotein pathway, which comprises the apoB100-containing lipoproteins, allows the transport of lipids from the liver to peripheral tissues [46,[49][50][51][52][53][54][55].…”

Hypertriglyceridemia Associated With Abdominal Obesity

“…[3][4][5] Other factors, such as lipoprotein lipase (LPL), apolipoprotein E, and apolipoprotein A5 polymorphisms, may predominantly affect triglyceride-rich lipoprotein clearance either or both through transfer into less buoyant particles or through direct removal of the particle from the circulation.…”

“…2 Some factors may predominantly increase triglyceride-rich lipoprotein secretion as, for example, excessive food intake and insulin resistance. [3][4][5] Other factors, such as lipoprotein lipase (LPL), apolipoprotein E, and apolipoprotein A5 polymorphisms, may predominantly affect triglyceride-rich lipoprotein clearance either or both through transfer into less buoyant particles or through direct removal of the particle from the circulation. 2 The present view is that hypertriglyceridemia associated with abdominal obesity stems from a combination of enhanced triglyceride-rich lipoprotein secretion with some impairment of clearance.…”