High-density lipoproteins and non-alcoholic fatty liver disease
Background and aims: Non-alcoholic fatty liver disease (NAFLD), a high incidence liver pathology, is associated with a ∼1.5-fold higher cardiovascular disease risk. This phenomenon is generally attributed to the NAFLD-associated increase in circulating levels of pro-atherogenic apolipoprotein B100-c...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Atherosclerosis Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667089523000366 |
| _version_ | 1797671437750763520 |
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| author | Menno Hoekstra Miranda Van Eck |
| author_facet | Menno Hoekstra Miranda Van Eck |
| author_sort | Menno Hoekstra |
| collection | DOAJ |
| description | Background and aims: Non-alcoholic fatty liver disease (NAFLD), a high incidence liver pathology, is associated with a ∼1.5-fold higher cardiovascular disease risk. This phenomenon is generally attributed to the NAFLD-associated increase in circulating levels of pro-atherogenic apolipoprotein B100-containing small dense low-density lipoprotein and plasma hypertriglyceridemia. However, also a significant reduction in cholesterol transported by anti-atherogenic high-density lipoproteins (HDL) is frequently observed in subjects suffering from NAFLD as compared to unaffected people. In this review, we summarize data regarding the relationship between NAFLD and plasma HDL-cholesterol levels, with a special focus on highlighting potential causality between the NAFLD pathology and changes in HDL metabolism. Methods and results: Publications in PUBMED describing the relationship between HDL levels and NAFLD susceptibility and/or disease severity, either in human clinical settings or genetically-modified mouse models, were critically reviewed for subsequent inclusion in this manuscript. Furthermore, relevant literature describing effects on lipid loading in cultured hepatocytes of models with genetic alterations related to HDL metabolism have been summarized. Conclusions: Although in vitro observations suggest causality between HDL formation by hepatocytes and protection against NAFLD-like lipid accumulation, current literature remains inconclusive on whether relative HDL deficiency is actually driving the development of fatty liver disease in humans. In light of the current obesity pandemic and the associated marked rise in NAFLD incidence, it is of clear scientific and societal interest to gain further insight into the relationship between HDL-cholesterol levels and fatty liver development to potentially uncover the therapeutic potential of pharmacological HDL level and/or function modulation. |
| first_indexed | 2024-03-11T21:15:32Z |
| format | Article |
| id | doaj.art-fa9a10c731fa48989ff35ce7d7468ae2 |
| institution | Directory Open Access Journal |
| issn | 2667-0895 |
| language | English |
| last_indexed | 2024-03-11T21:15:32Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Atherosclerosis Plus |
| spelling | doaj.art-fa9a10c731fa48989ff35ce7d7468ae22023-09-29T04:45:26ZengElsevierAtherosclerosis Plus2667-08952023-09-01533341High-density lipoproteins and non-alcoholic fatty liver diseaseMenno Hoekstra0Miranda Van Eck1Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands; Pharmacy Leiden, Leiden, the Netherlands; Corresponding author. Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, the Netherlands.Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands; Pharmacy Leiden, Leiden, the NetherlandsBackground and aims: Non-alcoholic fatty liver disease (NAFLD), a high incidence liver pathology, is associated with a ∼1.5-fold higher cardiovascular disease risk. This phenomenon is generally attributed to the NAFLD-associated increase in circulating levels of pro-atherogenic apolipoprotein B100-containing small dense low-density lipoprotein and plasma hypertriglyceridemia. However, also a significant reduction in cholesterol transported by anti-atherogenic high-density lipoproteins (HDL) is frequently observed in subjects suffering from NAFLD as compared to unaffected people. In this review, we summarize data regarding the relationship between NAFLD and plasma HDL-cholesterol levels, with a special focus on highlighting potential causality between the NAFLD pathology and changes in HDL metabolism. Methods and results: Publications in PUBMED describing the relationship between HDL levels and NAFLD susceptibility and/or disease severity, either in human clinical settings or genetically-modified mouse models, were critically reviewed for subsequent inclusion in this manuscript. Furthermore, relevant literature describing effects on lipid loading in cultured hepatocytes of models with genetic alterations related to HDL metabolism have been summarized. Conclusions: Although in vitro observations suggest causality between HDL formation by hepatocytes and protection against NAFLD-like lipid accumulation, current literature remains inconclusive on whether relative HDL deficiency is actually driving the development of fatty liver disease in humans. In light of the current obesity pandemic and the associated marked rise in NAFLD incidence, it is of clear scientific and societal interest to gain further insight into the relationship between HDL-cholesterol levels and fatty liver development to potentially uncover the therapeutic potential of pharmacological HDL level and/or function modulation.http://www.sciencedirect.com/science/article/pii/S2667089523000366High-density lipoproteinFatty liver diseaseSteatohepatitisHepatocytesSteatosisLipoprotein metabolism |
| spellingShingle | Menno Hoekstra Miranda Van Eck High-density lipoproteins and non-alcoholic fatty liver disease Atherosclerosis Plus High-density lipoprotein Fatty liver disease Steatohepatitis Hepatocytes Steatosis Lipoprotein metabolism |
| title | High-density lipoproteins and non-alcoholic fatty liver disease |
| title_full | High-density lipoproteins and non-alcoholic fatty liver disease |
| title_fullStr | High-density lipoproteins and non-alcoholic fatty liver disease |
| title_full_unstemmed | High-density lipoproteins and non-alcoholic fatty liver disease |
| title_short | High-density lipoproteins and non-alcoholic fatty liver disease |
| title_sort | high density lipoproteins and non alcoholic fatty liver disease |
| topic | High-density lipoprotein Fatty liver disease Steatohepatitis Hepatocytes Steatosis Lipoprotein metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2667089523000366 |
| work_keys_str_mv | AT mennohoekstra highdensitylipoproteinsandnonalcoholicfattyliverdisease AT mirandavaneck highdensitylipoproteinsandnonalcoholicfattyliverdisease |