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Calvo et al. Omega-3 fatty acids in cardiovascular health

that of the Danish population. Thus, environmental expressed in adipose tissue and skeletal muscle. [73]
factors - namely dietary n-3 PUFA intake - may exert a When PPAR-α is activated by specific substrates like
preponderant impact on serum lipids. [68] PUFAs, it favors the synthesis of enzymes involved
in lipid catabolism. [74] Therefore, n-3 PUFA intake
Among these actions on lipid metabolism, the TAG- promotes the β-oxidation of fatty acids in peripheral
lowering effect has been found to be the most robust in tissues, which contributes to the catabolism of
large epidemiological studies; [69] however, it appears to circulating TAG in chylomicrons and VLDL-C. This
be largely modifiable by the overall dietary composition, results in diminished traffic of non-esterified fatty
as elevated carbohydrate and saturated fat intake may acids to hepatocytes, causing an additional reduction
surpass the effect of n-3 PUFAs due to increased TAG in the input of substrates for TAG synthesis, further
synthesis and storage. [69,70] In addition, the magnitude decreasing the hepatic production of VLDL-C. [72]
of the lipid-lowering effect of n-3 PUFAs depends on
each subject’s basal serum lipid levels, as greater Additionally, PUFAs downregulate the sterol regulatory
decreases are observed in subjects with higher TAG element-binding protein 1c (SREBP1c), which
levels. [70,71] modulates the expression of genes involved in the
synthesis of fatty acids and TAG. [75,76] PUFAs inhibit
The mechanisms by which n-3 PUFAs achieve SREBP1c activity in the liver by antagonizing the
these effects on TAG are related to the decrease liver X receptor alpha, a nuclear receptor found in
of their hepatic synthesis via competitive inhibition hepatocytes that regulates the synthesis of SREBP
of the enzymes involved, especially 1,2 diglyceride and the SREBP inhibitor protein. [77,78] Another reported
acyltransferase, which catalyzes the conversion genetic mechanism is the ability of PUFAs to inhibit
of diacylglycerides into TAG. [72] In addition, PUFAs the hepatic maturation of the carbohydrate-responsive
have high affinity for several peroxisome proliferator- element-binding protein, a transcription factor related
activated receptor (PPAR) subtypes, particularly to the expression of enzymes involved in TAG
PPAR-α, a nuclear transcription factor highly synthesis [79] [Figure 4].

Figure 4: Role of polyunsaturated fatty acids in triacylglyceride metabolism. PUFAs decrease TAG through various mechanisms: (1)
competitive inhibition of DAT; (2) activating PPAR-a, which promotes the transcription of enzymes involved in lipolysis and fatty acid
transport; (3) suppressing the activity of SREBP-1c which regulates the expression of genes involved in fatty acid and TAG synthesis.
PUFA: polyunsaturated fatty acid; DAT: 1,2 diglyceride acyltransferase; TAG: triacylglycerides; PPAR-a: peroxisome-proliferator activated
receptor alpha; RXR: retinoid X receptor; LXR-a: liver X receptor alpha; SREBP-1c: sterol regulatory element-binding protein 1c; SCAP:
SREBP inhibitor protein; PPRE: PPAR response elements
120 Vessel Plus ¦ Volume 1 ¦ September 26, 2017