Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus

Abstract

Objective-Treatment with liraglutide, a GLP-1 (glucagon-like peptide-1) agonist, has been shown to reduce postprandial lipidemia, an important feature of diabetic dyslipidemia. However, the underlying mechanisms for this effect remain unknown. This prompted us to study the effect of liraglutide on the metabolism of ApoB48 (apolipoprotein B48). Approach and Results-We performed an in vivo kinetic study with stable isotopes (D 8 -valine) in the fed state in 10 patients with type 2 diabetes mellitus before treatment and 6 months after the initiation of treatment with liraglutide (1.2 mg/d).We also evaluated, in mice, the effect of a 1-week liraglutide treatment on postload triglycerides and analysed in vitro on jejunum, the direct effect of liraglutide on the expression of genes involved in the biosynthesis of chylomicron.

Semaglutide improves postprandial glucose and lipid metabolism, and delays first‐hour gastric emptying in subjects with obesity

“…This was confirmed in humans by Vergès and colleagues, who recently reported on the effects of liraglutide on the metabolism of ApoB‐48 . Treatment with liraglutide significantly decreased postprandial hyperlipidaemia in subjects with T2D via a mechanism of reduced ApoB‐48 production and increased ApoB‐48 catabolism …”

“…In a series of studies in hamsters and mice, Hsieh and colleagues showed that the GLP‐1 receptor is essential for regulation of the intestinal lipid and lipoprotein metabolism, through control of intestinal lipoprotein synthesis and secretion . This was confirmed in humans by Vergès and colleagues, who recently reported on the effects of liraglutide on the metabolism of ApoB‐48 . Treatment with liraglutide significantly decreased postprandial hyperlipidaemia in subjects with T2D via a mechanism of reduced ApoB‐48 production and increased ApoB‐48 catabolism …”

“…It is plausible that, by reducing the serum concentration of ApoB-48, semaglutide in turn reduces the 40 This was confirmed in humans by Vergès and colleagues, who recently reported on the effects of liraglutide on the metabolism of ApoB-48. 41 Treatment with liraglutide significantly decreased postprandial hyperlipidaemia in subjects with T2D via a mechanism of reduced ApoB-48 production and increased ApoB-48 catabolism. 41 The frequency of obesity is reported to be greater in consumers of high-fat diets than in consumers of low-fat diets.…”

“…41 Treatment with liraglutide significantly decreased postprandial hyperlipidaemia in subjects with T2D via a mechanism of reduced ApoB-48 production and increased ApoB-48 catabolism. 41 The frequency of obesity is reported to be greater in consumers of high-fat diets than in consumers of low-fat diets. 42 Therefore, the demonstrable effect of semaglutide on blood lipids during a high-fat meal is highly relevant for subjects with obesity, who often consume energy-dense, high-fat foods that contribute to hyperlipidaemia.…”

Investigation of human apoB48 metabolism using a new, integrated non‐steady‐state model of apoB48 and apoB100 kinetics

“…It follows that development of a true picture of the physiology of TRLs requires investigation of the non-steadystate dynamics of chylomicron metabolism overlayered on the (near) steady-state system of VLDL kinetics. To date, this has been difficult to achieve and it has been necessary to use analytical approaches that are arguably over-simplistic and/or employ nonphysiological nutritional regimens [8][9][10][11]. For example, previous studies of apoB48 metabolism have utilized a continuous micro-meal feeding pattern to generate a quasisteady state or used a single metabolic compartment to represent chylomicron kinetics following a test meal [8,9,[12][13][14][15][16][17][18].…”