Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity
Obesity may impair protein synthesis rates and cause anabolic resistance to growth factors, hormones, and exercise, ultimately affecting skeletal muscle mass and function. To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24‐h fractional synthesis rates (2...
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| creator | Nilsson, Mats I. Dobson, Justin P. Greene, Nicholas P. Wiggs, Michael P. Shimkus, Kevin L. Wudeck, Elyse V. Davis, Amanda R. Laureano, Marissa L. Fluckey, James D. |
| description | Obesity may impair protein synthesis rates and cause anabolic resistance to growth factors, hormones, and exercise, ultimately affecting skeletal muscle mass and function. To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24‐h fractional synthesis rates (24‐h FSRs) in selected hind‐limb muscles of sedentary and resistance‐exercised lean and obese Zucker rats. Despite atrophied hind‐limb muscles (–28% vs. lean rats), 24‐h FSRs of mixed proteins were significantly higher in quadriceps (+18%) and red or white gastrocnemius (+22 or +38%, respectively) of obese animals when compared to lean littermates. Basal synthesis rates of myofibrillar (+8%) and mitochondrial proteins (–1%) in quadriceps were not different between phenotypes, while manufacture of cytosolic proteins (+12%) was moderately elevated in obese cohorts. Western blot analyses revealed a robust activation of p70S6k (+178%) and a lower expression of the endogenous mTOR inhibitor DEPTOR (–28%) in obese rats, collectively suggesting that there is an obesity‐induced increase in net protein turnover favoring degradation. Lastly, the protein synthetic response to exercise of mixed (–7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle‐ and subfraction‐specific desensitization to the anabolic stimulus of exercise in obese animals.—Nilsson, M. I., Dobson, J. P., Greene, N. P., Wiggs, M. P., Shimkus, K. L., Wudeck, E. V., Davis, A. R., Laureano, M. L., Fluckey, J. D., Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 27, 3905–3916 (2013). www.fasebj.org |
| doi_str_mv | 10.1096/fj.12-224006 |
| format | Article |
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To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24‐h fractional synthesis rates (24‐h FSRs) in selected hind‐limb muscles of sedentary and resistance‐exercised lean and obese Zucker rats. Despite atrophied hind‐limb muscles (–28% vs. lean rats), 24‐h FSRs of mixed proteins were significantly higher in quadriceps (+18%) and red or white gastrocnemius (+22 or +38%, respectively) of obese animals when compared to lean littermates. Basal synthesis rates of myofibrillar (+8%) and mitochondrial proteins (–1%) in quadriceps were not different between phenotypes, while manufacture of cytosolic proteins (+12%) was moderately elevated in obese cohorts. Western blot analyses revealed a robust activation of p70S6k (+178%) and a lower expression of the endogenous mTOR inhibitor DEPTOR (–28%) in obese rats, collectively suggesting that there is an obesity‐induced increase in net protein turnover favoring degradation. Lastly, the protein synthetic response to exercise of mixed (–7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle‐ and subfraction‐specific desensitization to the anabolic stimulus of exercise in obese animals.—Nilsson, M. I., Dobson, J. P., Greene, N. P., Wiggs, M. P., Shimkus, K. L., Wudeck, E. V., Davis, A. R., Laureano, M. L., Fluckey, J. D., Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. 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Lastly, the protein synthetic response to exercise of mixed (–7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle‐ and subfraction‐specific desensitization to the anabolic stimulus of exercise in obese animals.—Nilsson, M. I., Dobson, J. P., Greene, N. P., Wiggs, M. P., Shimkus, K. L., Wudeck, E. V., Davis, A. R., Laureano, M. L., Fluckey, J. D., Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 27, 3905–3916 (2013). www.fasebj.org</description><subject>Animals</subject><subject>DEPTOR</subject><subject>diabetes</subject><subject>fractional synthesis rates</subject><subject>Gene Expression Regulation - physiology</subject><subject>Male</subject><subject>muscle</subject><subject>Obesity - metabolism</subject><subject>Physical Conditioning, Animal - physiology</subject><subject>Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rats</subject><subject>Rats, Zucker</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - genetics</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</subject><subject>Sarcopenia - metabolism</subject><subject>TOR Serine-Threonine Kinases - genetics</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90DtPwzAUBWALgWgpbMwoIwMpficZS0UBqRJDYbb8lFIlcbEToP8eVymMDFd3-e7R1QHgGsE5ghW_d9s5wjnGFEJ-AqaIEZjzksNTMIVlhXPOSTkBFzFuIYQIIn4OJpiUkKaLKdgsVOdDK5tsF3xv6y7rh9D5Txsy2Zk0Uvmm1lmwsY697LTNep_Zbxt0HW2WfJRB-53tEvIqqX5_Cc6cbKK9Ou4ZeF89vi2f8_Xr08tysc41hYznhmNmsHGUq8oQxphGumJKVlwZW1FeVLzgqDSU4aJ0FSLGOUSJgQYjQogiM3A75qbXPwYbe9HWUdumkZ31QxSIUkJKynGR6N1IdfAxBuvELtStDHuBoDjUKNxWICzGGhO_OSYPqrXmD__2lkAxgq-6sft_w8Rq84AhLlL3h-gfWYR9gA</recordid><startdate>201310</startdate><enddate>201310</enddate><creator>Nilsson, Mats I.</creator><creator>Dobson, Justin P.</creator><creator>Greene, Nicholas P.</creator><creator>Wiggs, Michael P.</creator><creator>Shimkus, Kevin L.</creator><creator>Wudeck, Elyse V.</creator><creator>Davis, Amanda R.</creator><creator>Laureano, Marissa L.</creator><creator>Fluckey, James D.</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201310</creationdate><title>Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity</title><author>Nilsson, Mats I. ; Dobson, Justin P. ; Greene, Nicholas P. ; Wiggs, Michael P. ; Shimkus, Kevin L. ; Wudeck, Elyse V. ; Davis, Amanda R. ; Laureano, Marissa L. ; Fluckey, James D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4056-d625d2df46b9d3555c1c95ba96bde9467967618d45278f913dff143d0d21333b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>DEPTOR</topic><topic>diabetes</topic><topic>fractional synthesis rates</topic><topic>Gene Expression Regulation - physiology</topic><topic>Male</topic><topic>muscle</topic><topic>Obesity - metabolism</topic><topic>Physical Conditioning, Animal - physiology</topic><topic>Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rats</topic><topic>Rats, Zucker</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - genetics</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Sarcopenia - metabolism</topic><topic>TOR Serine-Threonine Kinases - genetics</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nilsson, Mats I.</creatorcontrib><creatorcontrib>Dobson, Justin P.</creatorcontrib><creatorcontrib>Greene, Nicholas P.</creatorcontrib><creatorcontrib>Wiggs, Michael P.</creatorcontrib><creatorcontrib>Shimkus, Kevin L.</creatorcontrib><creatorcontrib>Wudeck, Elyse V.</creatorcontrib><creatorcontrib>Davis, Amanda R.</creatorcontrib><creatorcontrib>Laureano, Marissa L.</creatorcontrib><creatorcontrib>Fluckey, James D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nilsson, Mats I.</au><au>Dobson, Justin P.</au><au>Greene, Nicholas P.</au><au>Wiggs, Michael P.</au><au>Shimkus, Kevin L.</au><au>Wudeck, Elyse V.</au><au>Davis, Amanda R.</au><au>Laureano, Marissa L.</au><au>Fluckey, James D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2013-10</date><risdate>2013</risdate><volume>27</volume><issue>10</issue><spage>3905</spage><epage>3916</epage><pages>3905-3916</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Obesity may impair protein synthesis rates and cause anabolic resistance to growth factors, hormones, and exercise, ultimately affecting skeletal muscle mass and function. To better understand muscle wasting and anabolic resistance with obesity, we assessed protein 24‐h fractional synthesis rates (24‐h FSRs) in selected hind‐limb muscles of sedentary and resistance‐exercised lean and obese Zucker rats. Despite atrophied hind‐limb muscles (–28% vs. lean rats), 24‐h FSRs of mixed proteins were significantly higher in quadriceps (+18%) and red or white gastrocnemius (+22 or +38%, respectively) of obese animals when compared to lean littermates. Basal synthesis rates of myofibrillar (+8%) and mitochondrial proteins (–1%) in quadriceps were not different between phenotypes, while manufacture of cytosolic proteins (+12%) was moderately elevated in obese cohorts. Western blot analyses revealed a robust activation of p70S6k (+178%) and a lower expression of the endogenous mTOR inhibitor DEPTOR (–28%) in obese rats, collectively suggesting that there is an obesity‐induced increase in net protein turnover favoring degradation. Lastly, the protein synthetic response to exercise of mixed (–7%), myofibrillar (+6%), and cytosolic (+7%) quadriceps subfractions was blunted compared to the lean phenotype (+34, +40, and +17%, respectively), indicating a muscle‐ and subfraction‐specific desensitization to the anabolic stimulus of exercise in obese animals.—Nilsson, M. I., Dobson, J. P., Greene, N. P., Wiggs, M. P., Shimkus, K. L., Wudeck, E. V., Davis, A. R., Laureano, M. L., Fluckey, J. D., Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 27, 3905–3916 (2013). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>23804240</pmid><doi>10.1096/fj.12-224006</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals DEPTOR diabetes fractional synthesis rates Gene Expression Regulation - physiology Male muscle Obesity - metabolism Physical Conditioning, Animal - physiology Proteins - metabolism Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Zucker Ribosomal Protein S6 Kinases, 70-kDa - genetics Ribosomal Protein S6 Kinases, 70-kDa - metabolism Sarcopenia - metabolism TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism |
| title | Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity |
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