Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility.
Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and ofte...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4546114?pdf=render |
| _version_ | 1811305704375451648 |
|---|---|
| author | Shian-Huey Chiang W Wallace Harrington Guizhen Luo Naphtali O Milliken John C Ulrich Jing Chen Deepak K Rajpal Ying Qian Tiffany Carpenter Rusty Murray Robert S Geske Stephen A Stimpson Henning F Kramer Curt D Haffner J David Becherer Frank Preugschat Andrew N Billin |
| author_facet | Shian-Huey Chiang W Wallace Harrington Guizhen Luo Naphtali O Milliken John C Ulrich Jing Chen Deepak K Rajpal Ying Qian Tiffany Carpenter Rusty Murray Robert S Geske Stephen A Stimpson Henning F Kramer Curt D Haffner J David Becherer Frank Preugschat Andrew N Billin |
| author_sort | Shian-Huey Chiang |
| collection | DOAJ |
| description | Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet. |
| first_indexed | 2024-04-13T08:31:11Z |
| format | Article |
| id | doaj.art-6c250288d3cf48f0b41fe25918c4ad63 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T08:31:11Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6c250288d3cf48f0b41fe25918c4ad632022-12-22T02:54:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013492710.1371/journal.pone.0134927Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility.Shian-Huey ChiangW Wallace HarringtonGuizhen LuoNaphtali O MillikenJohn C UlrichJing ChenDeepak K RajpalYing QianTiffany CarpenterRusty MurrayRobert S GeskeStephen A StimpsonHenning F KramerCurt D HaffnerJ David BechererFrank PreugschatAndrew N BillinNicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet.http://europepmc.org/articles/PMC4546114?pdf=render |
| spellingShingle | Shian-Huey Chiang W Wallace Harrington Guizhen Luo Naphtali O Milliken John C Ulrich Jing Chen Deepak K Rajpal Ying Qian Tiffany Carpenter Rusty Murray Robert S Geske Stephen A Stimpson Henning F Kramer Curt D Haffner J David Becherer Frank Preugschat Andrew N Billin Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. PLoS ONE |
| title | Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. |
| title_full | Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. |
| title_fullStr | Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. |
| title_full_unstemmed | Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. |
| title_short | Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility. |
| title_sort | genetic ablation of cd38 protects against western diet induced exercise intolerance and metabolic inflexibility |
| url | http://europepmc.org/articles/PMC4546114?pdf=render |
| work_keys_str_mv | AT shianhueychiang geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT wwallaceharrington geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT guizhenluo geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT naphtaliomilliken geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT johnculrich geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT jingchen geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT deepakkrajpal geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT yingqian geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT tiffanycarpenter geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT rustymurray geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT robertsgeske geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT stephenastimpson geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT henningfkramer geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT curtdhaffner geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT jdavidbecherer geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT frankpreugschat geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility AT andrewnbillin geneticablationofcd38protectsagainstwesterndietinducedexerciseintoleranceandmetabolicinflexibility |