Fads1 and 2 are promoted to meet instant need for long-chain polyunsaturated fatty acids in goose fatty liver

Abstract

Global prevalence of non-alcoholic fatty liver disease (NAFLD) constitutes a threat to human health. Goose is a unique model of NAFLD for discovering therapeutic targets as its liver can develop severe steatosis without overt injury. Fatty acid desaturase (Fads) is a potential therapeutic target as Fads expression and mutations are associated with liver fat. Here, we hypothesized that Fads was promoted to provide a protection for goose fatty liver. To test this, goose Fads1 and Fads2 were sequenced. Fads1/2/6 expression was determined in goose liver and primary hepatocytes by quantitative PCR. Liver fatty acid composition was also analyzed by gas chromatography. Data indicated that hepatic Fads1/2/6 expression was gradually increased with the time of overfeeding. In contrast, trans-C18:1n9 fatty acid (Fads inhibitor) was reduced. However, enhanced Fads capacity for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis was not sufficient to compensate for the depleted LC-PUFAs in goose fatty liver. Moreover, cell studies showed that Fads1/2/6 expression was regulated by fatty liver-associated factors. Together, these findings suggest Fads1/2 as protective components are promoted to meet instant need for LC-PUFAs in goose fatty liver, and we propose this is required for severe hepatic steatosis without liver injury.

Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice

“…However, several conditions can significantly diminish the capacity of the liver for LCPUFA synthesis from their precursors thus affecting the hepatic levels of n-6 n-3 LCPUFAs, including (i) the lack of nutrients such as zinc [35]; (ii) the excessive ethanol consumption [36]; and (iii) the existence of certain polymorphisms in the gene sequences of Δ-5 and Δ-6 desaturases that reduces the activity of these enzymes [37]. An interesting situation related to the activity of Δ-5 and Δ-6 desaturases is liver steatosis, a pathological condition in which the oxidative stress of nutritional origin generated by fat overload (lipotoxicity) also results in a reduction in the desaturation capacity of the tissue with low levels of n-6 and n-3 LCPUFAs [14, 38, 39], effects that are also observed after a HFD [15, 40]. Also, in overfeeding conditions the increment in gene expression of Δ-5 and Δ-6 desaturase enzymes is not sufficient to compensate the reduction of n-6 and n-3 LCPUFAs [39].…”

“…The substantial diminution in the hepatic levels of LCPUFAs by HFD, particularly those from the n-3 series (EPA, DHA and DPA), may be ascribed to the drastic reduction of the liver activity of desaturase enzymes achieved, considering their relevance in LCPUFA metabolism [15, 40]. This effect can be contributed by the diminution in the hepatic levels of the n-3 LCPUFA precursor ALA observed (Table 2) and by the enhancement in the oxidative stress status of the liver (Fig.…”

Identification of differentially expressed miRNAs in the fatty liver of Landes goose (Anser anser)

“…Domestic Palmipedes are particularly susceptible to hepatic steatosis, and unlike human NAFLD, the fatty liver is nonpathological and reversible 16 . Goose liver has been widely studied by researchers as a good model to investigate the mechanism of lipid metabolism 17 . Since the miRNAs involved in fatty liver production in geese remain to be elucidated, an analysis of the functional miRNAs involved in goose hepatic steatosis was performed on.…”

Role of the stearyl-coenzyme A desaturase 1 gene in regulating palmitic acid tolerance of goose primary hepatocytes

“…In another study, Iwai et al [10] found that SCD1 affected apoptosis in mouse proximal tubular cells by regulating the MUFAs/SFAs ratio. Moreover, it was found that in overfeeding-induced goose fatty liver, the MUFAs/SFAs ratio significantly increased while the content of both palmitic acid and stearic acids decreased [4,11]. Thus, it can be generalized that SCD1 exerts an important role in regulating MUFAs/SFAs ratio.…”

“…In poultry production, this capacity is exploited for producing the fatty liver that is 5-to 10-fold larger than normal liver after 2-3 weeks of overfeeding [2,3]. Interestingly, its liver can develop serious steatosis without overt injury [4], showing minimal inflammation and other immune-related responses, which suggests that goose has different physiological and metabolic characteristics from mammals. In a previous study, the mRNA levels of tumor necrosis factor alpha (TNFα) was significantly downregulated by overfeeding in the goose liver [5].…”