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.

Dyslipidemia is a major risk factor for cardiovascular disease, and its impact may be exacerbated when accompanied by metabolic dysfunction-associated steatotic liver disease (MASLD). The simultaneous management of these conditions poses multiple challenges for healthcare providers. Insulin resistance has been implicated in the pathogenesis of both dyslipidemia and MASLD, necessitating a holistic approach to managing dyslipidemia, glucose levels, body weight, and MASLD. This review explores the intricate pathophysiological relationship between MASLD and dyslipidemia. It also examines current guidance regarding the use of lipid-lowering agents (including statins, ezetimibe, fibrates, omega-3 polyunsaturated fatty acids, and proprotein convertase subtilisin/kexin type 9 inhibitors) as well as glucose-lowering medications (such as pioglitazone, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors) in patients with MASLD, with or without metabolic dysfunction-associated steatohepatitis (MASH), and dyslipidemia. Additionally, the review addresses the potential of emerging drugs to concurrently target both MASLD/MASH and dyslipidemia. Our hope is that a deeper understanding of the mechanisms underlying MASLD and dyslipidemia may assist clinicians in the management of these complex cases.

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.

Dyslipidemia is a major risk factor for cardiovascular disease, and its impact may be exacerbated when accompanied by metabolic dysfunction-associated steatotic liver disease (MASLD). The simultaneous management of these conditions poses multiple challenges for healthcare providers. Insulin resistance has been implicated in the pathogenesis of both dyslipidemia and MASLD, necessitating a holistic approach to managing dyslipidemia, glucose levels, body weight, and MASLD. This review explores the intricate pathophysiological relationship between MASLD and dyslipidemia. It also examines current guidance regarding the use of lipid-lowering agents (including statins, ezetimibe, fibrates, omega-3 polyunsaturated fatty acids, and proprotein convertase subtilisin/kexin type 9 inhibitors) as well as glucose-lowering medications (such as pioglitazone, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors) in patients with MASLD, with or without metabolic dysfunction-associated steatohepatitis (MASH), and dyslipidemia. Additionally, the review addresses the potential of emerging drugs to concurrently target both MASLD/MASH and dyslipidemia. Our hope is that a deeper understanding of the mechanisms underlying MASLD and dyslipidemia may assist clinicians in the management of these complex cases.

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.

Dyslipidemia is a major risk factor for cardiovascular disease, and its impact may be exacerbated when accompanied by metabolic dysfunction-associated steatotic liver disease (MASLD). The simultaneous management of these conditions poses multiple challenges for healthcare providers. Insulin resistance has been implicated in the pathogenesis of both dyslipidemia and MASLD, necessitating a holistic approach to managing dyslipidemia, glucose levels, body weight, and MASLD. This review explores the intricate pathophysiological relationship between MASLD and dyslipidemia. It also examines current guidance regarding the use of lipid-lowering agents (including statins, ezetimibe, fibrates, omega-3 polyunsaturated fatty acids, and proprotein convertase subtilisin/kexin type 9 inhibitors) as well as glucose-lowering medications (such as pioglitazone, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors) in patients with MASLD, with or without metabolic dysfunction-associated steatohepatitis (MASH), and dyslipidemia. Additionally, the review addresses the potential of emerging drugs to concurrently target both MASLD/MASH and dyslipidemia. Our hope is that a deeper understanding of the mechanisms underlying MASLD and dyslipidemia may assist clinicians in the management of these complex cases.

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.

Dyslipidemia is a major risk factor for cardiovascular disease, and its impact may be exacerbated when accompanied by metabolic dysfunction-associated steatotic liver disease (MASLD). The simultaneous management of these conditions poses multiple challenges for healthcare providers. Insulin resistance has been implicated in the pathogenesis of both dyslipidemia and MASLD, necessitating a holistic approach to managing dyslipidemia, glucose levels, body weight, and MASLD. This review explores the intricate pathophysiological relationship between MASLD and dyslipidemia. It also examines current guidance regarding the use of lipid-lowering agents (including statins, ezetimibe, fibrates, omega-3 polyunsaturated fatty acids, and proprotein convertase subtilisin/kexin type 9 inhibitors) as well as glucose-lowering medications (such as pioglitazone, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors) in patients with MASLD, with or without metabolic dysfunction-associated steatohepatitis (MASH), and dyslipidemia. Additionally, the review addresses the potential of emerging drugs to concurrently target both MASLD/MASH and dyslipidemia. Our hope is that a deeper understanding of the mechanisms underlying MASLD and dyslipidemia may assist clinicians in the management of these complex cases.