Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus

Abstract

This article is available online at http://www.jlr.orgThe insulin-resistance state and type 2 diabetes mellitus (T2DM) are closely related with an increase in cardiovascular disease. Factors conditioning this increase in cardiovascular disease include metabolic dyslipidemia associated with insulin resistance. It has recently been suggested that the overproduction of intestinally derived apolipoprotein (apo)B48-containing lipoproteins may contribute greatly to the dyslipidemia found in both the fasting and postprandial states in insulin resistance ( 1-3 ). However, the underlying mechanisms are still not fully understood.Most studies undertaken in this area have been carried out in the postprandial state ( 3, 4 ). The intestine maintains a basal production of apoB48, even in fasting states, synthesizing small triglyceride-rich lipoprotein (TRL) particles ( 4, 5 ). Animal studies have shown that the contribution of intestinal lipoproteins to the total fasting plasma triglycerides is from 10% to 20% ( 4, 5 ), increasing in the case of diabetes ( 4, 6, 7 ). Fructose-fed hamsters experience an increase in the assembly and secretion of apoB48-containing lipoproteins in insulin-resistant states ( 2 ). Duez et al. showed that the production of chylomicrons (CM) was upregulated in humans with insulin resistance ( 8 ). Studies undertaken in fructose-fed, insulin-resistant Syrian golden hamsters in both the fasted and fed states found that, in these insulin-resistant animals, the increased production of small TRL was greater in the fasted state than the fed state ( 1 ). Nevertheless, caution should be exercised when extrapolating results from experimental animal models to humans, due to the differences between species.Abstract The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the infl uence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides ( P < 0.001) and apolipoprotein (apo)B48 ( P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content ( P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression ( P = 0.043). However, the apoA-IV mRNA expression was signifi cantly greater ( P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression ( r = ؊ 0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These fi ndings show that the jejunum appears to play an act...

The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance

“…26 At the same time, the results of the expression of intestinal MTTP are contradictory. A previous study conducted in humans showed no significant changes in intestinal MTTP expression in morbidly obese subjects with T2DM, 3 whereas other studies show that there is an increase in intestinal MTTP expression in a rabbit model of diabetes 27 and in insulin-resistant non-diabetic Zucker obese fa/fa rats. 28 However, there is little information regarding MTTP in humans.…”

“…3 The mucosa was washed with physiological saline solution, scraped, immediately frozen in liquid nitrogen, and maintained at − 80°C until analysis. Other jejunal biopsies from the morbidly obese subjects group with low HOMA-IR were taken to isolate intestinal epithelial cells (IEC) (n = 6).…”

“…Serum biochemical variables were measured in duplicate, as previously described. 3,[11][12][13] Apo B-48 was analyzed by enzyme immunoassay (ELISA) (Shibayagi Co., Japan). Cross-reaction with human apolipoprotein B-100 was less than the lower detection limit.…”

“…3 There is a growing body of evidence that in the fasting state, the intestine synthesizes small triglyceriderich lipoprotein, maintaining a basal production of apo B-48. 4 Also, it has been shown that elevated fasting chylomicron levels are present in obese and hyperlipidemic subjects.…”

“…We have previously shown that morbidly obese subjects with type 2 diabetes had lower jejunal lipid content in fasting status than non-diabetic morbidly obese subjects, and that this correlated negatively with apolipoprotein A-IV (apo A-IV) mRNA expression. 3 Apo A-IV has an important role in enhancing the secretion of chylomicrons and associated lipids in newborn enterocytes. 6 A dysregulation of intestinal lipoprotein metabolism in insulin-resistant states has also been shown in animal models 7 and humans.…”