Author
Maria Cristina Zingaretti
Bio: Maria Cristina Zingaretti is an academic researcher from Marche Polytechnic University. The author has contributed to research in topics: Adipose tissue & White adipose tissue. The author has an hindex of 19, co-authored 27 publications receiving 5545 citations.
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TL;DR: This article showed that PGC1α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin.
Abstract: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.
3,338 citations
TL;DR: It is demonstrated that human adults indeed possess BAT and thus imply possibilities of future therapeutic strategies for the treatment of obesity, including maintenance of brown adipocytes and stimulation of the growth of preexisting brown precursors.
Abstract: Classically, adult humans have been considered not to possess active brown adipose tissue (BAT). However, positron-emission-tomography has shown fluorodeoxyglucose uptake that is distributed in such a way (e.g., in the neck) that it would seem to be BAT. Until now this has not been supported by direct evidence that these areas truly represented BAT, that is, the presence of the BAT-unique uncoupling protein-1 (UCP1). Samples of adipose tissue from the neck of 35 patients undergoing surgery for thyroid diseases were obtained and analyzed. In 1/3 of the subjects (the younger and leaner), distinct islands composed of UCP1 immunoreactive brown adipocytes could clearly be discerned, accounting for up to 1/3 of all adipocytes. The brown-adipose islands were richly sympathetically innervated (indicating acute central control); adjacent white adipose areas were not. The capillary density was high, implying a high capacity for oxygen delivery. Cells with features of brown adipocyte precursors were found in pericapillary areas. These data demonstrate that human adults indeed possess BAT and thus imply possibilities of future therapeutic strategies for the treatment of obesity, including maintenance of brown adipocytes and stimulation of the growth of preexisting brown precursors.
699 citations
TL;DR: It is hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins: most come from convertible unilocular lipidocytes that becomeMultilocular and make many mitochondria that contain UCP3, and some come from a cell that gives rise to more typical brown adipocytes that express UCP1.
Abstract: Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL) Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3 Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1
567 citations
TL;DR: Quantitative analysis showed that cold acclimation induced an increase in brown adipocytes and an almost equal reduction in white adipocytes; however, there were no significant differences in total adipocyte count or any signs of apoptosis or mitosis, in line with the hypothesis of the direct transformation of white into Brown adipocytes.
394 citations
TL;DR: It is found that murine endothelial cells of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes, suggesting an endothelial origin of murine and human adipocytes.
320 citations
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TL;DR: This article showed that PGC1α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin.
Abstract: Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.
3,338 citations
TL;DR: The results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology and that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids.
Abstract: How much does the microbiota influence the host's phenotype? Ridaura et al. ([1241214][1] ; see the Perspective by [ Walker and Parkhill ][2]) obtained uncultured fecal microbiota from twin pairs discordant for body mass and transplanted them into adult germ-free mice. It was discovered that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Moreover, obese-phenotype mice were invaded by members of the Bacteroidales from the lean mice, but, happily, the lean animals resisted invasion by the obese microbiota.
[1]: http://www.sciencemag.org/content/341/6150/1241214.full
[2]: /lookup/doi/10.1126/science.1243787
2,929 citations
TL;DR: Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin, providing evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes.
2,767 citations
TL;DR: The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.
Abstract: Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination.
2,404 citations
TL;DR: Interest in adipogenesis has increased markedly over the past few years with emphasis on the intersection between extracellular signals and the transcriptional cascade that regulates adipocyte differentiation.
Abstract: Improved knowledge of all aspects of adipose biology will be required to counter the burgeoning epidemic of obesity. Interest in adipogenesis has increased markedly over the past few years with emphasis on the intersection between extracellular signals and the transcriptional cascade that regulates adipocyte differentiation. Many different events contribute to the commitment of a mesenchymal stem cell to the adipocyte lineage including the coordination of a complex network of transcription factors, cofactors and signalling intermediates from numerous pathways.
2,363 citations