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Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats
Lu Zheng1, Yuehua Feng1, Yuanping Shi1
1Comprehensive Laboratory, the Third Affiliated Hospital of Soochow University, Changzhou, P.R. China.
Background:
Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels.
Aims:
To assess the effects of increased free fatty acids (FFAs) levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression.
Methods:
Adult male Sprague-Dawley (SD) rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR) were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK) rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array.
Results:
Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8) was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin.
Conclusion:
These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.
Insights
Increased free fatty acids (FFAs) from Intralipid infusion reduced hepatic apolipoprotein M (ApoM) levels and insulin sensitivity. ApoM overexpression improved insulin tolerance, suggesting ApoM modulation as a therapeutic strategy for insulin resistance.
Area of Science:
- Metabolic research
- Lipid metabolism
- Gene expression analysis
Background:
- Apolipoprotein M (ApoM) is a key component of high-density lipoproteins (HDL) involved in reverse cholesterol transport.
- Insulin resistance, a hallmark of type 2 diabetes, is linked to diminished ApoM levels.
Purpose of the Study:
- To investigate the impact of elevated free fatty acids (FFAs) on insulin sensitivity and hepatic ApoM gene expression.
- To explore the therapeutic potential of modulating ApoM levels in the context of insulin resistance.
Main Methods:
- Adult male Sprague-Dawley rats received Intralipid infusions to elevate FFAs.
- Hyperinsulinemic-euglycemic clamps assessed glucose infusion rates (GIR) to measure insulin sensitivity.
- Human embryonic kidney 293T cells and Goto-Kakizaki rats were used to study ApoM overexpression effects on insulin tolerance and gene expression via real-time RT-PCR and PCR array.
Main Results:
- Intralipid infusion significantly increased plasma FFAs and decreased insulin sensitivity (GIR).
- Hepatic ApoM gene expression was notably reduced following Intralipid treatment.
- Overexpression of ApoM in Goto-Kakizaki rats enhanced the glucose-lowering effects of insulin, indicating improved insulin tolerance.
Conclusions:
- Short-term Intralipid infusion leads to decreased hepatic ApoM levels and exacerbates insulin resistance.
- ApoM overexpression demonstrates a promising role in ameliorating insulin resistance in vivo.
- Targeting ApoM expression presents a potential therapeutic avenue for managing insulin resistance in type 2 diabetes.
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