Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats

PLoS One. 2014 Aug 21;9(8):e105681. doi: 10.1371/journal.pone.0105681. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins / genetics*
  • Apolipoproteins / metabolism*
  • Apolipoproteins M
  • Fatty Acids, Nonesterified / blood
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance* / genetics
  • Lipocalins / genetics*
  • Lipocalins / metabolism*
  • Liver / metabolism
  • Male
  • PPAR delta / genetics
  • PPAR delta / metabolism
  • PPAR-beta / genetics
  • PPAR-beta / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Signal Transduction

Substances

  • APOM protein, human
  • Apolipoproteins
  • Apolipoproteins M
  • Fatty Acids, Nonesterified
  • Insulin
  • Lipocalins
  • PPAR delta
  • PPAR-beta
  • RNA, Messenger

Grants and funding

This research project was supported by the National Natural Science Foundation of China (NSFC) (81071414, 81201352, http://www.nsfc.gov.cn/), the Natural Science Foundation of Jiangsu Province (BK2011245, BK2012154, http://www.jskjjh.gov.cn/) and a research grant from the Changzhou Science & Technology Bureau (CJ20122012, http://new.czstb.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.