Physiology and pathophysiology of liver lipid metabolism

Abstract

Liver lipid metabolism and its modulation are involved in many pathologic conditions, such as obesity, non-alcoholic fatty liver disease, diabetes mellitus, atherosclerosis and cardiovascular disease. Metabolic disorders seem to share a similar background of low-grade chronic inflammation, even if the pathophysiological mechanisms leading to tissue and organ damage have not been completely clarified yet. The accumulation of neutral lipids in the liver is now recognized as a beneficial and protective mechanism; on the other hand, lipoperoxidation is involved in the development and progression of non-alcoholic steatohepatitis. The role of the gut microbiota in liver lipid metabolism has been the object of recent scientific investigations. It is likely that the gut microbiota is involved in a complex metabolic modulation and the translocation of gut microflora may also contribute to maintaining the low-grade inflammatory status of metabolic syndrome. Therefore, lipid metabolism pathology has vague limits and complex mechanisms, and the knowledge of these is essential to guide diagnostic and therapeutic decisions.

Keywords:

• cardiovascular disease
• cholesterol
• gut microbiota
• liver lipid metabolism
• metabolic syndrome
• NAFLD
• NASH

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• The hepatic lipid content is the result of uptake, storage, re-arrangement, outflow and synthesis, finely regulated by complex metabolic mechanisms.

• The pathology of liver lipid metabolism has not only local consequences (fibrosis/cirrhosis), but is part of a large network involving insulin resistance and linked to cardiovascular pathology.

• Non-alcoholic fatty liver disease represents a health problem for 30% of the general adult population and for 70–80% of diabetic and obese patients, who therefore have an altered hepatic lipid metabolism.

• Metabolic syndrome and non-alcoholic fatty liver disease share a similar pathologic background of low-grade chronic inflammation.

• Non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) are well-distinct manifestations of deregulated hepatic lipid metabolism, inflammation, lipotoxicity and fibrosis (recognizable in NASH since the beginning) being the main differences.

• Lipoperoxidation and the consequent accumulation of reactive oxygen species are the main causes of FA-related toxicity; hepatic cytokines and adipokines such as IL-6, TNF-α, leptin, adiponectin, PPARs and the endocannabinoid system are involved in the development of NASH and its progression.

• Gut microbiota is involved in the metabolism of dietary choline, which is a structural component of lipoproteins, thus affecting the secretion of VLDLs and promoting hepatic lipid accumulation, lipoperoxidation and insulin resistance.

• Gut microbiota may modulate hepatic and systemic fat storage by modifying bile acids structure, thus interfering with their function in lipid absorption and with their indirect impact on lipoperoxidation.

• Gut microbiota translocation induces local inflammation in the liver but also in the adipocytes, heart, vessels and others various tissues, realizing a kind of metabolic infection, which might contribute to the low grade inflammatory status characterizing metabolic syndrome.

Notes