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The present study examines whether and to what extent the profiles of proteolytic-related genes are altered in atrophying muscle during prolonged food deprivation. Long-term fasted animals exhibited three metabolic phases characterized by changes in lipid and protein utilization. Starvation induced an increase in some proteolytic gene expressions during P2 of fasting, especially for Cat L (by 3-fold). In P3, the fasting-induced enhancement of mRNA expression involved all proteolytic pathways and was much more pronounced than in P2 for pUb, E2(14k), CAPN3, and Cat B, D, and H (by 2- to 4-fold), for C2, C5, and S5a (by 5- to 6-fold), and mainly for Cat L, C3, and C8 (by 10- to 15-fold). At the molecular level, it is concluded that the three proteolytic systems found in skeletal muscle are selectively induced in P2 of fasting and coordinately upregulated in late fasting.
Many hypothalamic neuropeptides are involved in the regulation of energy homeostasis and feeding behavior. We have investigated whether and to what extent neuropeptide Y (NPY), agouti-related protein (AGRP), melanin-concentrating hormone (MCH), and prepro-orexin (prepro-OX) as well as pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) mRNA levels are affected in rat hypothalamus. An experimental model of long-term fasting rat characterized by three metabolic phases from changes in lipid and protein utilization was used. Except for prepro-OX and compared to fed group, starvation induced an increase in the orexigenic gene expressions that was much more marked in phase 3 (by 2.5-, 8.1-, and 13.5-fold for MCH, AGRP, and NPY, respectively) than in phase 2 (by about 1.5-2.2-fold as an average) of fasting. AGRP and NPY mRNA levels were inversely related to body fat content. Anorexigenic gene expression was only slightly affected at both fasting stages. We conclude that the regulation of NPY and AGRP gene expression is primarily involved during late fasting and could mediate the concomitant enhanced drive for refeeding.
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