| 1. |
- de Jong, Jasper M. A., et al.
(författare)
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Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice
- 2019
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 1:8, s. 830-843
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Tidskriftsartikel (refereegranskat)abstract
- Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 degrees C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.
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| 2. |
- Scheele, Camilla, et al.
(författare)
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Altered regulation of the PINK1 locus: a link between Type 2 diabetes and neurodegeneration?
- 2007
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 21:13, s. 3653-3665
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in PINK1 cause the mitochondrial-related neurodegenerative disease Parkinson’s. Here we investigate whether obesity, type 2 diabetes, or inactivity alters transcription from the PINK1 locus. We utilized a cDNA-array and quantitative real-time PCR for gene expression analysis of muscle from healthy volunteers following physical inactivity, and muscle and adipose tissue from nonobese or obese subjects with normal glucose tolerance or type 2 diabetes. Functional studies of PINK1 were performed utilizing RNA interference in cell culture models. Following inactivity, the PINK1 locus had an opposing regulation pattern (PINK1 was down-regulated while natural antisense PINK1 was up-regulated). In type 2 diabetes skeletal muscle, all transcripts from the PINK1 locus were suppressed and gene expression correlated with diabetes status. RNA interference of PINK1 in human neuronal cell lines impaired basal glucose uptake. In adipose tissue, mitochondrial gene expression correlated with PINK1 expression although remained unaltered following siRNA knockdown of Pink1 in primary cultures of brown preadipocytes. In conclusion, regulation of the PINK1 locus, previously linked to neurodegenerative disease, is altered in obesity, type 2 diabetes and inactivity, while the combination of RNAi experiments and clinical data suggests a role for PINK1 in cell energetics rather than in mitochondrial biogenesis.
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| 3. |
- Zenius Jespersen, Naja, et al.
(författare)
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A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans
- 2013
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 17:5, s. 798-805
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Tidskriftsartikel (refereegranskat)abstract
- Human brown adipose tissue (BAT) has been detected in adults but was recently suggested to be of brite/beige origin. We collected BAT from the supraclavicular region in 21 patients undergoing surgery for suspected cancer in the neck area and assessed the gene expression of established murine markers for brown, brite/beige, and white adipocytes. We demonstrate that a classical brown expression signature, including upregulation of miR-206, miR-133b, LHX8, and ZIC1 and downregulation of HOXC8 and HOXC9, coexists with an upregulation of two newly established brite/beige markers, TBX1 and TMEM26. A similar mRNA expression profile was observed when comparing isolated human adipocytes from BAT and white adipose tissue (WAT) depots, differentiated in vitro. In conclusion, our data suggest that human BAT might consist of both classical brown and recruitable brite adipocytes, an observation important for future considerations on how to induce human BAT.
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