Molecular Regulation of Lipogenesis, Adipogenesis and Fat Deposition in Chicken

Abstract

In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer's health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic selection, feeding strategies, housing, and environmental strategies, as well as hormone supplementation. Recent investigations at the molecular level have revealed the significant role of the transcriptional and post-transcriptional regulatory networks and their interaction on modulating fat metabolism in chickens. At the transcriptional level, different transcription factors are known to regulate the expression of lipogenic and adipogenic genes through various signaling pathways, affecting chicken fat metabolism. Alternatively, at the post-transcriptional level, the regulatory mechanism of microRNAs (miRNAs) on lipid metabolism and deposition has added a promising dimension to understand the structural and functional regulatory mechanism of lipid metabolism in chicken. Therefore, this review focuses on the progress made in unraveling the molecular function of genes, transcription factors, and more notably significant miRNAs responsible for regulating adipogenesis, lipogenesis, and fat deposition in chicken. Moreover, a better understanding of the molecular regulation of lipid metabolism will give researchers novel insights to use functional molecular markers, such as miRNAs, for selection against excessive fat deposition to improve chicken production efficiency and meat quality.

Keywords: adipogenesis; chicken; fat deposition; lipogenesis; meat quality; post-transcriptional regulation; transcriptional regulation.

Figure 1

Schematic representation of de novo lipogenesis in chicken hepatocyte and its regulation at the transcriptional and post-transcriptional level. Red, orange, and green lines indicated the targets of various miRNAs, sterol response element-binding protein (SREBP1) as a transcription factor, and hormones in the chicken hepatocyte, respectively. PK, pyruvate kinase enzyme; TCA, tricarboxylic acid cycle; ACLY, ATP-citrate lyase; ACC, acetyl-CoA carboxylase; MD, malate dehydrogenase; NADPH, nicotinamide adenine dinucleotide phosphate; ME, malic enzyme; FASN, fatty acid synthase; ELOVL6, ELOVL fatty acid elongase 6; SCD, stearoyl-CoA desaturase; FADS, fatty acid desaturase; FA-CoA, fatty acid-acyl-CoA; ACSL, long-chain acyl-CoA synthetases; G3P, glycerol-3-phosphate; GPAT, glycerophosphate acyltransferase; AGPAT, acylglycerophosphate acyltransferase; LPIN, lipid phosphate phosphohydrolase; DGAT, diacylglycerol acyltransferase; MTTP, microsomal triglyceride transfer protein; VLDL, very-low-density lipoprotein; SFA, saturated fatty acid; USFA, unsaturated fatty acids; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; FFA, free fatty acids.

Figure 2

Schematic representation of adipogenesis and fat deposition and their regulation at the transcriptional and post-transcriptional level in the chicken adipocyte. Several regulatory factors, including hormones (green boxes), transcriptional factors (blue boxes), miRNAs (red boxes), and their target genes, controlling adipogenesis and fat deposition in chicken. 1—Adipogenesis (orange boxes) is the process of differentiation in which mesenchymal cells turn into mature adipocytes. 2—The fatty acids released from VLDL can penetrate adipocytes, which inside adipocytes resynthesized into TG and deposited. Accumulated fat in chicken adipose tissue consists of TG either from plasma VLDL (source 1) or from dietary fats (portomicrons) (source 2). 3—The presence of exogenous fatty acids (from VLDL or diet) is vital for regulating the expression of peroxisome proliferator-activated receptor-γ (PPARγ). 4—The blue boxes revealed the sequence of transcriptional factors controlling adipogenesis; the early transcriptional regulators, including CCAAT/Enhancer binding-protein (C/EBPβ and C/EBPδ) express and stimulate the key transcription factors, including PPARγ and C/EBPα which at terminal differentiation stage, regulate the transcriptional regulation of a variety of adipocyte-associated genes, such as lipoprotein lipase (LPL), fatty-acid-binding proteins (FABP), cluster of differentiation 36 (CD36), and adiponectin, C1Q and collagen domain-containing (ADIPOQ). PPARγ and C/EBPα are the master regulators of adipogenesis that can crossregulate each other. Sterol response element-binding protein (SREBP1) is regulated by insulin and can regulate adipogenesis by inspiration the expression of PPARγ through adipogenesis. Kruppel-like transcription factor (KLF5) is activated by C/EBPβ/δ through the early stages of adipogenesis and then promotes the expression of PPARγ. KLF2 and GATA binding protein 2 (GATA2) are the anti-adipogenic transcription factors, which lead to adipogenesis repression through inhibition of the expression of PPARγ. Zinc finger protein 423 (Zfp423) regulates preadipocyte cell determination through regulation of PPARγ expression. 5—The red boxes indicated various significantly expressed miRNAs with regulatory effects on adipogenesis. 6—Fat deposition in chicken is mediated and regulated by different signaling pathways (purple boxes), including the PPAR signaling pathway and the cell junction pathways (focal adhesions, tight junction, ECM-receptor interaction, regulation of actin cytoskeleton). The cell junction-related pathways may mediate the PPAR signaling pathway after activating PPARγ. Then PPARγ upregulates the expression of lipogenic-related genes, such as FABP3, LPL. The steroid biosynthesis pathway through regulating the expression of genes, such as 24-dehydrocholesterol reductase (DHCR24) and NAD(P) dependent steroid dehydrogenase-like (NSDHL), might play a dominant role in fat deposition in chicken (). Open arrows and diamond arrows represented the stimulating and inhibition effects, respectively.

Figure 3

Differentially expressed miRNA through chicken intramuscular preadipocyte differentiation in the breast muscle between juvenile and late-laying hen. Overexpression of gga-miR-140-5p reduced the expression of retinoid X receptor γ (RXRG) while upregulated the expression of adipogenic markers, including the peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid-binding protein 4 (FABP4); promoting intramuscular preadipocyte differentiation and IMF deposition in chickens [7]. Controversy, overexpression of gga-miR-223, as a negative regulator of chicken intramuscular preadipocyte differentiation, significantly reduced the expression of its target gene glycerol-3-phosphate acyltransferase (GPAM), as well as PPARγ and FAPB4, and lead to intramuscular preadipocyte differentiation inhibition and decrease the number of IMF droplets in the adipocyte [52].

Figure 4

The potential network of signaling pathways contributing to the chicken lipid metabolism. The above-mentioned pathways (gray boxes) might be the crucial pathways for lipid deposition in chicken breast muscle. Activation of PPARγ in the PPAR signaling pathway leads to upregulation of lipogenic genes, including ADIPOQ, LPL, SCD, or CD36, to promote TG synthesis. Moreover, PPARγ may promote the interaction of PLIN1with CIDEC to accelerate LD formation. Meanwhile, upregulation of cholesterol synthesis genes, such as DHCR24 and NSDHL, in the steroid biosynthesis pathway may upgrade the steroid ester synthesis. Ses, Sterol esters; TGs, Triglycerides; LD, lipid droplet; PLIN, Perilipins; PPARγ, peroxisome proliferator-activated receptor γ; ADIPOQ, adiponectin; LPL, lipoprotein lipase; SCD, stearoyl-CoA desaturase; CD36, cluster of differentiation 36; DHCR24, 24-dehydrocholesterol reductase; NSDHL, NAD (P) dependent steroid dehydrogenase-like; LSS, Lanosterol synthase; MSMO1, Methylsterol monooxygenase 1; CH25H, Cholesterol 25-hydroxylase. Black, red, and green arrows indicate possible regulatory relationship, bidirectional regulatory relationship, and reported regulatory relationship, respectively. Figure 4 was adapted from [23] with permission.