title: Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness.
abstract: Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.
authors: Department of Experimental, Diagnostic and Specialty Medicine and Interdepartmental Centre L Galvani, CIG, University of Bologna, Bologna, Italy. m.conte@unibo.it
authors: Maria
authors: M
authors: Conte
authors: Francesco
authors: F
authors: Vasuri
authors: Giovanni
authors: G
authors: Trisolino
authors: Elena
authors: E
authors: Bellavista
authors: Aurelia
authors: A
authors: Santoro
authors: Alessio
authors: A
authors: Degiovanni
authors: Ermanno
authors: E
authors: Martucci
authors: Antonia
authors: A
authors: D'Errico-Grigioni
authors: Daniela
authors: D
authors: Caporossi
authors: Miriam
authors: M
authors: Capri
authors: Andrea B
authors: AB
authors: Maier
authors: Olivier
authors: O
authors: Seynnes
authors: Laura
authors: L
authors: Barberi
authors: Antonio
authors: A
authors: Musarò
authors: Marco V
authors: MV
authors: Narici
authors: Claudio
authors: C
authors: Franceschi
authors: Stefano
authors: S
authors: Salvioli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D053580:Muscle Strength; D018908:Muscle Weakness / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000070780:Perilipin-2; D055948:Sarcopenia / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I
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