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Apolipoprotein M
Guanghua Luo1, Xiaoying Zhang, Peter Nilsson-Ehle
1Department of Clinical Chemistry, Institute of Laboratory Medicine, University Hospital of Lund, S-221 85 Lund, Sweden. shineroar@163.com
Abstract:
Apolipoprotein M (apoM) is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL) in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL). Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse). Human apoM cDNA (734 base pairs) encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF) and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1alpha (HNF-1alpha) is an activator of apoM gene promoter. Deficiency of HNF-1alpha mouse shows lack of apoM expression. Mutations in HNF-1alpha (MODY3) have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob) mouse or leptin receptor deficient (db/db) mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.
Insights
Apolipoprotein M (apoM) is a protein found in human plasma, primarily linked to HDL. Its expression is regulated by factors like HNF-1alpha and leptin, impacting conditions such as MODY3 and obesity.
Area of Science:
- Lipid metabolism and lipoprotein research
- Gene expression and regulation
- Human genetics and disease
Background:
- Apolipoprotein M (apoM) is a 26-kDa protein primarily associated with high-density lipoprotein (HDL) in human plasma.
- A small fraction of apoM is also found in triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL).
- The human apoM gene is located on chromosome 6, and the protein belongs to the lipocalin superfamily.
Purpose of the Study:
- To investigate the tissue-specific expression of apolipoprotein M.
- To identify regulatory factors influencing apoM gene expression.
- To explore the potential role of apoM in metabolic diseases like MODY3 and obesity.
Main Methods:
- Human tissue expression array analysis to determine apoM expression sites.
- In situ hybridization to localize apoM mRNA in hepatocytes and kidney tubule cells.
- Analysis of apoM expression in genetically modified mouse models (apoA-I deficient, HNF-1alpha deficient, leptin deficient, leptin receptor deficient).
Main Results:
- ApoM is predominantly expressed in the liver and kidney, specifically in hepatocytes and kidney tubule epithelial cells.
- Platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), and leptin can regulate apoM expression.
- ApoM expression is significantly reduced in apoA-I deficient, HNF-1alpha deficient, leptin deficient (ob/ob), and leptin receptor deficient (db/db) mice.
- Mutations in Hepatocyte nuclear factor-1alpha (HNF-1alpha), associated with MODY3, lead to reduced serum apoM levels.
- Plasma apoM concentration correlates positively with leptin levels in obese individuals.
Conclusions:
- Apolipoprotein M expression is tightly regulated by specific transcription factors and hormones.
- ApoM plays a role in lipid metabolism and may be implicated in the pathogenesis of MODY3 and obesity.
- Further research into apoM's function could offer insights into metabolic disease treatment.
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