EXTRACELLULAR MATRIX IN MUSCLE REGENERATION, ADIPOSE TISSUE FUNCTION AND MEAT QUALITY

Xiangdong Liu

doi:10.7273/000004476

Extracellular matrix (ECM) is an important constituent of tissues and organs. However, abundant ECM deposition leads to fibrosis. Obesity has become a pandemic around the world, which results in serious diseases, including fibrosis of muscle and adipose tissue. The skeletal muscle and adipose tissue fibrosis is closely correlated with metabolic dysfunction. Additionally, the content and structure of ECM affect the meat tenderness, a main determinant of meat quality. A better understanding of the mechanism in which ECM development and accumulation is necessary for the development of therapeutic for obesity-associated metabolic dysfunctions and meat quality improvement. In this dissertation, three studies are included: (1) AMP-activated protein kinase (AMPK) is a potent inhibitor of fibrosis, which is down-regulated due to obesity. Our data showed that AMPK deletion in fibrotic/adipogenic progenitors (FAPs) impaired muscle regeneration with increased fibrosis. AMPKα1 knockout in FAPs enhanced p65 translocation to nuclei, which increased the expression of MMP-9. MMP-9 cleaved latent-TGF-β, releasing active TGF-β. Active TGF-β elevated the apoptosis-resistance and fibrotic commitment of FAPs, resulting in fibrosis of regenerated muscle. (2) Lysyl oxidase (LOX), a key enzyme catalyzing collagen cross-linking. AMPK regulates LOX via suppressing TGF-β/SMADs signaling. We found that obesity increased mature nonreducible collagen cross-linking in white adipose tissue (WAT) of mice, which is positively associated with insulin resistance. In addition, enhanced TGF-β due to inactivation of AMPK under the obese condition promoted phosphorylation of SMAD3, the expression of LOX and other fibrogenic genes in white adipose tissue. Moreover, in vivo, AMPK activation suppressed TGF-β1-induced LOX expression and fibrosis. (3) The late gestation is critical for intramuscular fat and connective tissue development, therefore, maternal diet during this stage has an important effect on the offspring beef quality. Besides, breed is another player of meat quality. We tested the effect of breed, Angus versus Wagyu, and dietary protein levels of cows during the late gestation on the offspring beef quality. Our results showed that a mild restriction of protein diet during late gestation had no major effect on beef quality. Furthermore, Wagyu- sired cattle had higher tenderness, marbling score, and less collagen cross-linking products than Angus- sired cattle.

EXTRACELLULAR MATRIX IN MUSCLE REGENERATION, ADIPOSE TISSUE FUNCTION AND MEAT QUALITY

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