Short-term, high-fat diet increases the expression of key intestinal genes involved in lipoprotein metabolism in healthy men

et al. 2020

Diabetol Metab Syndr

Self Cite

Background: Evidence suggests that pathophysiological conditions such as obesity and type 2 diabetes (T2D) are associated with morphologic and metabolic alterations in the small intestinal mucosa. Exploring these alterations generally requires invasive methods, limiting data acquisition to subjects with enteropathies or undergoing bariatric surgery. We aimed to evaluate small intestine epithelial cell homeostasis in a cohort of men covering a wide range of adiposity and glucose homoeostasis statuses. Methods: Plasma levels of citrulline, a biomarker of enterocyte mass, and I-FABP, a biomarker of enterocyte death, were measured by UHPLC-MS and ELISA in 154 nondiabetic men and 67 men with a T2D diagnosis. Results: Plasma citrulline was significantly reduced in men with insulin resistance and T2D compared to insulin sensitive men. Decreased citrulline levels were, however, not observed in men with uncontrolled metabolic parameters during T2D. Plasma I-FABP was significantly higher in men with T2D, especially in presence of uncontrolled glycemic and lipid profile parameters. Integration of both parameters, which estimate enterocyte turnover, was associated with glucose homeostasis as well as with T2D diagnosis. Differences in biomarkers levels were independent of age and BMI and glucose filtration rates. Conclusions: Our study supports a decreased functional enterocyte mass and an increased enterocyte death rate in presence of metabolic alterations but emphasizes that epithelial cell homeostasis is especially altered in presence of severe insulin resistance and T2D. The marked changes in small intestine cellularity observed in obesity and diabetes are thus suggested to be part of gut dysfunctions, mainly at an advanced stage of the disease.

Section: Study Populationmentioning

confidence: 99%

Plasma biomarkers of small intestine adaptations in obesity-related metabolic alterations

Lalande

Drouin‐Chartier

et al. 2020

Diabetol Metab Syndr

Self Cite

“…Total RNA was then eluted into 100 l RNase-free H 2 O and stored at Ϫ 80°C. RNA quantifi cation and quantitative real-time PCR were performed as described ( 28 ).…”

Section: Total Rna Extraction Rna Quantifi Cation and Quantitative mentioning

confidence: 99%

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

Couture

Journal of Lipid Research

Kelly

et al. 2014

Self Cite

Dyslipidemia is an important feature of insulin resistance (IR) that contributes to the pathogenesis of atherosclerosis and increases the risk of cardiovascular disease ( 1 ). Dyslipidemia associated with IR is typically characterized by elevated concentrations of triglyceride-rich lipoproteins (TRLs), reduced plasma levels of HDL-cholesterol (HDL-C), an increased number of small dense LDL particles, and greater levels of free fatty acid (FFA) ( 1 ). Metabolic kinetic studies have indicated that the increased plasma levels of TRLs in individuals with IR are caused by the elevated secretion of both hepatic (apoB-100-containing) and intestinal (apoB-48-containing) lipoproteins in fasting and postprandial states ( 2-5 ). We have already shown that the intestinal lipoprotein production rate (PR) is markedly greater in dyslipidemic patients with type 2 diabetes ( 6 ). This relationship is of signifi cant interest because there is now convincing evidence indicating that elevated levels of intestine-derived lipoproteins are proatherogenic and associated with an increased risk of cardiovascular disease ( 7-9 ). Hence, a better understanding of the factors regulating intestinal lipoprotein secretion could potentially lead to rational therapeutic strategies to reduce cardiovascular risk in this vulnerable group of patients. Abstract Insulin resistance (IR) is

“…The expression of the housekeeping gene glucose-6-phosphate-dehydrogenase (G6PD) was used as a reference. The intestinal expressions of ACS1 and SAR1B were quantified in n ϭ 95 and n ϭ 84 subjects, respectively, whereas the expressions of SREBP1c, FATP4, FABP2, ACS1, DGAT1, DGAT2, The validity of the intestinal gene expression model used in the present study was demonstrated in previous studies by the interrelationship of the expression of coregulated genes (5,9,10,39,41,42). The validity of the intestinal gene expression model is also supported by positive associations between the expression of the gene and the mass of the protein in biopsy samples, as previously reported (5,42).…”

Section: Methodsmentioning

confidence: 55%

“…The present study is a cross-sectional analysis of data from 127 male subjects who participated in intestinal gene expression studies in our laboratory (5,9,10,39,41,42). These studies were approved by the Laval University Ethical Review Committee, and written consent was obtained from all subjects.…”

Section: Methodsmentioning

confidence: 99%

Differential associations between plasma concentrations of insulin and glucose and intestinal expression of key genes involved in chylomicron metabolism

Drouin‐Chartier

American Journal of Physiology-Gastrointestinal and Liver Physi

Lemelin

et al. 2018

Self Cite

The mechanisms underlying the oversecretion of apolipoprotein (apo)B-48-containing triglyceride-rich lipoproteins (TRL) in insulin-resistance (IR) states in humans remain to be fully understood. The objective of this study was to evaluate the association between the plasma levels of insulin and glucose and the intestinal expression of key genes involved in chylomicron metabolism in a large sample of nondiabetic men displaying various degrees of IR. Duodenal biopsies were obtained by gastroduodenoscopy in 127 men free of intestinal disease. Gene expression was measured using quantitative PCR in duodenal samples. Plasma insulin and glucose concentrations were measured in the fasting state. Postprandial TRL apoB-48 kinetics were measured using a primed-constant infusion of l-[5,5,5-D]leucine for 12 h in a subgroup of 75 subjects maintained in a constant fed state. Plasma insulin levels were negatively associated with intestinal expression of ACS1 (standard β = -0.20, P = 0.007), DGAT1 (β = -0.18, P = 0.001), DGAT2 (β = -0.20, P = 0.02), and MTP (β = -0.27, P = 0.0005), whereas glucose levels were positively associated with MTP expression (β = 0.15, P = 0.04) independent of age, BMI, waist circumference, dietary intake, and duodenal expression of SREBP1c. Insulin levels, but not glucose concentrations, were positively correlated with postprandial TRL apoB-48 production rate ( r = 0.24, P = 0.04) and pool size ( r = 0.27, P = 0.03). In conclusion, plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism. These results suggest that alterations in intestinal lipoprotein metabolism associated with IR may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency. NEW & NOTEWORTHY We demonstrate that plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism in men. For instance, intestinal expression of MTP is negatively associated with plasma insulin concentrations and positively associated with plasma glucose concentrations. Alterations in intestinal lipoprotein metabolism associated with insulin resistance may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency.