Date of Graduation

12-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Kinesiology (PhD)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor

Tyrone A. Washington

Committee Member

Nicholas P. Greene

Second Committee Member

Cynthia Sides

Third Committee Member

Walter Bottje

Fourth Committee Member

Jeffrey Wolchok

Keywords

Biological sciences; Health and environmental sciences; Aging; Inflammation; Obesity; Regeneration; Sarcopenia; Skeletal muscle

Abstract

AIM: Sarocpenic obesity is a national concern within the United States because this metabolic syndrome is tied with reduced mobility and quality of life. Both obesity and aging are associated with insulin-resistance, chronic low-grade inflammation and muscle weakness. Skeletal muscle regeneration is a process that involves the coordinated effort of myogenic regulatory factors (MRFs), inflammatory signaling, and extracellular matrix (ECM) remodeling for optimal regeneration. It has been demonstrated that obesity and aging have a reduction in muscle regeneration. It has not been examined if sarcopenic obesity will further reduce muscle mass and the regenerative process. The purpose of this study was to determine how sarcopenic obesity alters inflammatory signaling and extracellular remodeling in mouse skeletal muscle. METHODS: One hundred two male C57BL6/J mice (4 weeks old) were randomly assigned to either a high fat diet (HFD, 60% fat) or normal chow. Both young (3 months old) and aged mice (22-24 months old) were injected with either PBS or bupivacaine. Muscles were excised 3 or 21 days after injection. RESULTS: Mean cross-sectional area was reduced by 26% in aged HFD mice. The aged lean mice had 9% greater mean cross-sectional area 21 days following muscle damage but no changes were observed in aged HFD. Aged mice had nearly 2-fold collagen III content than young mice. P-STAT3/STAT3 was reduced by 82% in the aged HFD mice in the TA. NF-κB was 3-5 fold greater in the aged HFD mice compared to the aged lean mice in the gastrocnemius and the TA. There was a main effect of injury to reduce collagen I and III content in aged injured, and a main effect of diet with a decrease of collagen I, collagen III, and MMP-9 gene expression in aged HFD mice 3 days following muscle damage. CONCLUSION: Sarcopenic obese mice have reduced cross-sectional area than aged lean mice along with increased collagen III content and basal alterations in MyoD, ECM proteins, and inflammation gene expression. During skeletal muscle regeneration sarocopenic obese mice had dysregulated inflammatory signaling and reduced ECM gene expression. These data suggest further impairment in the regenerative process in sarcopenic obese mice.

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