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. 2012 May;1821(5):843-51.
doi: 10.1016/j.bbalip.2011.10.011. Epub 2011 Oct 25.

Fish Oil -- How Does It Reduce Plasma Triglycerides?

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Free PMC article

Fish Oil -- How Does It Reduce Plasma Triglycerides?

Gregory C Shearer et al. Biochim Biophys Acta. .
Free PMC article

Abstract

Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle β-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

Figures

Figure 1
Figure 1. FA transport and FO induced changes
FAs are transported throughout the body in two major forms: esterified in TG carried by VLDL (VLDL-TG) and non-esterified carried by serum albumin (NEFA). From these two pools FA are distributed to different tissues depending on energy requirements and hormonal status. In the tissues, FA are used for ATP production via β-oxidation, re-esterification in TG for energy storage, incorporation into lipids composing cell membranes, and production of signaling molecules. Non-essential FA can also be de novo synthesized from other carbon sources. The liver (top left) acts as a major site for FA distribution, processing FAs from all sources: diet, de novo lipogenesis, circulating NEFA and VLDL remnants, and producing VLDL-TG which are secreted into the circulation. Adipose tissue (right) is the main storage depot for FA (as TG storage in lipid droplets). Adipocyte uptake of FAs from the circulation occurs via LpL lipolysis of VLDL-TG. Adipocytes largely contribute to the plasma NEFA pool by regulated release of FA from lipid droplets via HSL-lipolysis. Adipose tissue macrophages (bottom right) regulate intracellular lipolysis in adipocytes by secreting inflammatory cytokines. Heart and skeletal muscle (bottom left) obtain FAs from the NEFA pool and from the VLDL-TG pool via LpL-lipolysis. β-oxidation plays a major role in FA disposal in the heart and skeletal muscle. In hepatocytes, FO (a) down-regulates VLDL production and (b) up-regulates β-oxidation; in adipocytes, FO (c) increases FA uptake from LpL lipolysis of plasma TG, (d) decreases intracellular lipolysis in adipocytes, and (e) increases β-oxidation; FO also (f) reduces the secretion of pro-inflammatory cytokines from adipose tissue macrophages; in heart and skeletal muscle, FO (g) up-regulates LPL lipolysis of plasma TG and (h) β-oxidation. Pathways enhanced by FO are indicated by bold arrows, and those reduced by FO are indicated by dotted arrows. Abbreviations: FA – fatty acid, GPCR – g-protein coupled receptor; LpL – lipoprotein lipase; NEFA – non-esterified fatty acid; PPAR – peroxisome proliferator-activated receptor; VLDL – very-low density lipoprotein.

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