| 1. |
- Alkhori, Liza, et al.
(författare)
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The corepressor Atrophin specifies odorant receptor expression in Drosophila
- 2014
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Ingår i: The FASEB Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 28:3, s. 1355-1364
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Tidskriftsartikel (refereegranskat)abstract
- In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses one odorant receptor (OR) from a large genomic repertoire. How a receptor is specified is a tantalizing question addressing fundamental aspects of cell differentiation. Here, we demonstrate that the corepressor Atrophin (Atro) segregates OR gene expression between OSN classes in Drosophila. We show that the knockdown of Atro result in either loss or gain of a broad set of ORs. Each OR phenotypic group correlated with one of two opposing Notch fates, Notch responding, Nba (N(on)), and nonresponding, Nab (N(off)) OSNs. Our data show that Atro segregates ORs expressed in the Nba OSN classes and helps establish the Nab fate during OSN development. Consistent with a role in recruiting histone deacetylates, immunohistochemistry revealed that Atro regulates global histone 3 acetylation (H3ac) in OSNs and requires Hdac3 to segregate OR gene expression. We further found that Nba OSN classes exhibit variable but higher H3ac levels than the Nab OSNs. Together, these data suggest that Atro determines the level of H3ac, which ensures correct OR gene expression within the Nba OSNs. We propose a mechanism by which a single corepressor can specify a large number of neuron classes.-Alkhori, L., Öst, A., Alenius, M. The corepressor Atrophin specifies odorant receptor expression in Drosophila.
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| 2. |
- Öst, Anita, 1965-, et al.
(författare)
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Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes
- 2010
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Ingår i: Molecular Medicine. - : Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 16:07-Aug, s. 235-246
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Tidskriftsartikel (refereegranskat)abstract
- The protein kinase mammalian target of rapamycin (mTOR) mediates insulin control ofprotein synthesis, autophagy, mitochondrial function, and, through feedback signaling tophosphorylation of IRS1 at serine residues, mTOR directly controls insulin signaling. Weshow that in adipocytes from patients with type 2 diabetes (T2D) insulin activation of mTORis attenuated and that the resultant phenotype is compatible with, and can be mimicked by,loss of mTOR activation. In T2D adipocytes mitochondrial function is impaired andautophagy strongly upregulated, with concomitant increased autophagic destruction ofmitochondria and lipofuscin particles, and a dependence on autophagy for ATP production.Conversely, mitochondrial dysfunction attenuates insulin activation of mTOR, enhancesautophagy and attenuates feedback to IRS1. Our findings put mTOR in the driver´s seat of aninsulin resistance that in adipocytes can be fuelled by mitochondrial dysfunction,inflammation, ER-stress, or hypoxia.
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| 3. |
- Öst, Anita, et al.
(författare)
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Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity
- 2014
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Ingår i: Cell. - : Elsevier (Cell Press). - 0092-8674 .- 1097-4172. ; 159:6, s. 1352-1364
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Tidskriftsartikel (refereegranskat)abstract
- The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution.
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| 4. |
- Östh, Martin, et al.
(författare)
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The Concentration of beta-Carotene in Human Adipocytes, but Not the Whole-Body Adipocyte Stores, Is Reduced in Obesity
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:1, s. 85610-
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the concentration of beta-carotene in the fat of isolated abdominal subcutaneous adipocytes obtained from lean (BMIless than23 kg/m(2)), non-obese with higher BMI (23 less than= BMIless than28 kg/m(2)), obese (BMI greater than= 28 kg/m(2)), and from a group of obese subjects with type 2 diabetes. The concentration of b-carotene was 50% lower in the adipocytes from the obese and obese/diabetic groups compared with the lean and non-obese groups. Interestingly, the total amount of beta-carotene in the adipocyte stores of each subject was constant among all groups. Triacylglycerol constituted 92 +/- 1% (by weight) of the adipocyte lipids in the lean group and this was increased to 99 +/- 2% in the obese group with diabetes (pless than0.05). The concentration of cholesteryl esters was in all cases less than0.1 g per 100 g of total lipids, demonstrating that mature human adipocytes have negligible stores of cholesteryl ester. Our findings demonstrate that adipocyte concentrations of beta-carotene are reduced in obese subjects. The lower concentrations in adipocytes from subjects with type 2 diabetes apparently reflect subjects obesity. Our finding that whole-body stores of beta-carotene in adipocytes are constant raises new questions regarding what function it serves, as well as the mechanisms for maintaining constant levels in the face of varied adipose tissue mass among individuals over a period of time.
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