McCourt 2016 PLOS ONE: Difference between revisions
(Created page with "{{Publication |title=McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmรฉr E, Bjรถrkqvist M (2016) White adipose tissue browning in the R6/2 mouse model of Huntington's dise...") ย |
No edit summary |
||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmรฉr E, Bjรถrkqvist M (2016) White adipose tissue browning in the R6/2 mouse model of Huntington's disease. PLOS ONE 11:e0159870. ย | |title=McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmรฉr E, Bjรถrkqvist M (2016) White adipose tissue browning in the R6/2 mouse model of Huntington's disease. PLOS ONE 11:e0159870. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/27486903 PMID: 27486903 Open Access] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/27486903 PMID: 27486903 Open Access] | ||
|authors=McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmer E, Bjoerkqvist M | |authors=McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmer E, Bjoerkqvist M | ||
|year=2016 | |year=2016 | ||
|journal=PLOS ONE | |journal=PLOS ONE | ||
|abstract=Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1). UCP1 enables dissociation of cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT has been suggested to enhance energy expenditure. In this study, we therefore investigated the gene expression profile, histological appearance, response to cold challenge and functional aspects of WAT in the R6/2 HD mouse model and selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from R6/2 mice contained significantly more brown-like adipocyte regions and had a gene profile suggestive of the presence of brown-like adipocytes, such as higher ''Ucp1'' expression. Cold exposure induced ''Ucp1'' expression in R6/2 inguinal WAT to a markedly higher degree as compared to the thermogenic response in WT WAT. Alongside this, gene expression of transcription factors (''Zfp516'' and ''Pparฮฑ''), important inducers of WAT browning, were increased in R6/2 inguinal WAT, and ''Creb1'' was highlighted as a key transcription factor in HD. In addition to increased WAT ''Ucp1'' expression, a trend towards increased mitochondrial oxygen consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT. Key gene expressional changes (increased expression of (''Zfp516'' and ''Pparฮฑ'')) were replicated in inguinal WAT obtained from Q175 mice. In summary, for the first time, we here show that HD mouse WAT undergoes a process of browning, resulting in molecular and functional alterations that may contribute to the weight loss and altered metabolism observed with disease progression. ย | |abstract=Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1). UCP1 enables dissociation of cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT has been suggested to enhance energy expenditure. In this study, we therefore investigated the gene expression profile, histological appearance, response to cold challenge and functional aspects of WAT in the R6/2 HD mouse model and selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from R6/2 mice contained significantly more brown-like adipocyte regions and had a gene profile suggestive of the presence of brown-like adipocytes, such as higher ''Ucp1'' expression. Cold exposure induced ''Ucp1'' expression in R6/2 inguinal WAT to a markedly higher degree as compared to the thermogenic response in WT WAT. Alongside this, gene expression of transcription factors (''Zfp516'' and ''Pparฮฑ''), important inducers of WAT browning, were increased in R6/2 inguinal WAT, and ''Creb1'' was highlighted as a key transcription factor in HD. In addition to increased WAT ''Ucp1'' expression, a trend towards increased mitochondrial oxygen consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT. Key gene expressional changes (increased expression of (''Zfp516'' and ''Pparฮฑ'')) were replicated in inguinal WAT obtained from Q175 mice. In summary, for the first time, we here show that HD mouse WAT undergoes a process of browning, resulting in molecular and functional alterations that may contribute to the weight loss and altered metabolism observed with disease progression. | ||
|mipnetlab=SE Lund Elmer E | |mipnetlab=SE Lund Elmer E | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, nDNA;cell genetics, Exercise physiology;nutrition;life style | |area=Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Fat | |tissues=Fat | ||
|preparations= | |preparations=Permeabilized cells | ||
|injuries=Temperature | |injuries=Temperature | ||
|diseases=Neurodegenerative | |diseases=Neurodegenerative | ||
|couplingstates= | |couplingstates=LEAK, OXPHOS, ETS | ||
|substratestates=CI&II, ROX | |substratestates=CI&II, ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2016-10 | ||
}} | }} |
Revision as of 11:21, 2 November 2016
McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmรฉr E, Bjรถrkqvist M (2016) White adipose tissue browning in the R6/2 mouse model of Huntington's disease. PLOS ONE 11:e0159870. |
McCourt AC, Jakobsson L, Larsson S, Holm C, Piel S, Elmer E, Bjoerkqvist M (2016) PLOS ONE
Abstract: Huntington's disease (HD) is a fatal, autosomal dominantly inherited neurodegenerative disorder, characterised not only by progressive cognitive, motor and psychiatric impairments, but also of peripheral pathology. In both human HD and in mouse models of HD there is evidence of increased energy expenditure and weight loss, alongside altered body composition. Unlike white adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1). UCP1 enables dissociation of cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT has been suggested to enhance energy expenditure. In this study, we therefore investigated the gene expression profile, histological appearance, response to cold challenge and functional aspects of WAT in the R6/2 HD mouse model and selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from R6/2 mice contained significantly more brown-like adipocyte regions and had a gene profile suggestive of the presence of brown-like adipocytes, such as higher Ucp1 expression. Cold exposure induced Ucp1 expression in R6/2 inguinal WAT to a markedly higher degree as compared to the thermogenic response in WT WAT. Alongside this, gene expression of transcription factors (Zfp516 and Pparฮฑ), important inducers of WAT browning, were increased in R6/2 inguinal WAT, and Creb1 was highlighted as a key transcription factor in HD. In addition to increased WAT Ucp1 expression, a trend towards increased mitochondrial oxygen consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT. Key gene expressional changes (increased expression of (Zfp516 and Pparฮฑ)) were replicated in inguinal WAT obtained from Q175 mice. In summary, for the first time, we here show that HD mouse WAT undergoes a process of browning, resulting in molecular and functional alterations that may contribute to the weight loss and altered metabolism observed with disease progression.
โข O2k-Network Lab: SE Lund Elmer E
Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression, Exercise physiology;nutrition;life style
Pathology: Neurodegenerative
Stress:Temperature
Organism: Mouse
Tissue;cell: Fat
Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
2016-10