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The Isolation of Flowing Mesenteric Lymph in Mice to Quantify In Vivo Kinetics of Dietary Lipid Absorption and Chylomicron Secretion
Published on: November 30, 2022
Chylomicron Characteristics Are Associated With Microsomal Triglyceride Transfer Protein in an Animal Model of
Carolina Olano1,2, Gregorio Fariña1,2, Morena Wiszniewski3
1Laboratorio de Lípidos y Aterosclerosis, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Objective:
Intestinal remnant chylomicrons (CMs) are involved in cardiovascular residual risk and the atherogenic process. Microsomal triglyceride transfer protein (MTTP) catalyzes the assembly of lipids to apolipoprotein B48, generating CMs. Dysbiosis could alter this behavior. This study investigated the chemical composition of CMs and their associations with intestinal MTTP and gut fat depots in a diet-induced dysbiosis animal model.
Methods:
Male Wistar rats were fed either a standard diet (control, n=10) or a high-fat high-sucrose diet (HFSD, n=10) for 14 weeks. Measurements included serum glucose, lipid-lipoprotein profile, free fatty acids (FFAs), lipopolysaccharide (LPS) and the Firmicutes/Bacteroidetes (F/B) ratio in stool samples, via real-time quantitative polymerase chain reaction. Lipid content in isolated CMs (ultracentrifugation d <0.95 g/mL) was assessed, and MTTP, cell intestinal fat content (CIF), histology, apoB mRNA and tight junction (TJ) proteins were analyzed, in intestinal tissue.
Results:
Compared to control, HFSD rats showed higher levels of LPS, triglycerides (TGs), non-high-density lipoprotein cholesterol (HDL-C) levels, TG/HDL-C ratio, FFAs, and the F/B ratio. HFSD CMs showed increased TG and phospholipids. TJ proteins levels were lower in the HFSD group, while histological scores showed no differences. CIF was increased in the HFSD group. No significant differences in apoB mRNA were found. MTTP expression was higher in the HFSD group, and directly correlated with CM-TG and inversely correlated with CIF.
Conclusion:
Our findings imply that gut TG content may constitute an important determinant of the secretion of TG-rich CMs, promoted by MTTP, with increased atherogenic potential.
Insights
High-fat diets promote dysbiosis, increasing intestinal fat and triglyceride-rich chylomicrons (CMs). This suggests gut fat content influences CM secretion and atherogenic risk, mediated by microsomal triglyceride transfer protein (MTTP).
Area of Science:
- Metabolic Syndrome
- Gastroenterology
- Cardiovascular Research
Background:
- Intestinal remnant chylomicrons (CMs) contribute to cardiovascular residual risk and atherogenesis.
- Microsomal triglyceride transfer protein (MTTP) is crucial for CM assembly.
- Gut dysbiosis may influence CM metabolism.
Purpose of the Study:
- To investigate the chemical composition of CMs.
- To examine associations between CMs, intestinal MTTP, and gut fat depots.
- To utilize a diet-induced dysbiosis animal model.
Main Methods:
- Wistar rats were fed standard or high-fat high-sucrose diets (HFSD) for 14 weeks.
- Assessed serum lipids, FFAs, LPS, and gut microbiota (F/B ratio).
- Analyzed CM lipid content, intestinal MTTP, cell intestinal fat content (CIF), and tight junction proteins.
Main Results:
- HFSD rats exhibited higher LPS, TG, non-HDL-C, TG/HDL-C ratio, FFAs, and F/B ratio.
- HFSD CMs had increased TG and phospholipids; TJ proteins were lower.
- Intestinal MTTP expression was elevated in HFSD rats and correlated with CM-TG.
Conclusions:
- Gut triglyceride content is a key determinant of TG-rich CM secretion.
- MTTP activity, influenced by gut fat, promotes CMs with higher atherogenic potential.
- Diet-induced dysbiosis impacts CM composition and cardiovascular risk factors.
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