21 research outputs found
Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning
Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the
limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is
involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown
adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of
differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet
formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1.
Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy,
formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In
agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage,
adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its
brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by
PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a
new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that
both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.We thank FPLD2 patients for donating biological samples. We thank the Italian
Network for Laminopathies and the European Consortium of Lipodystrophies
(ECLip) for support and helpful discussion. We thank Aurelio Valmori for the
technical support. The studies were supported by Rizzoli Orthopedic Institute
â5 per milleâ 2014 project to MC, AIProSaB project 2016 and Fondazione Del
Monte di Bologna e Ravenna grant 2015â2016 âNew pharmacological
approaches in bone laminopathies based on the use of antibodies neutralizing
TGF beta 2â to GL. GL is also supported by PRIN MIUR project 2015FBNB5Y.S
Fundulus as the premier teleost model in environmental biology : opportunities for new insights using genomics
Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part D: Genomics and Proteomics 2 (2007): 257-286, doi:10.1016/j.cbd.2007.09.001.A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.This material is based on work supported by grants from the National Science Foundation DBI-0420504 (LJB), OCE 0308777 (DLC, RNW, BBR), BES-0553523 (AW), IBN 0236494 (BBR), IOB-0519579 (DHE), IOB-0543860 (DWT), FSML-0533189 (SC); National Institute of Health NIEHS P42-ES007381(GVC, MEH), P42-ES10356 (RTD), ES011588 (MFO); and NCRR P20 RR-016463 (DWT); Natural Sciences and Engineering Research Council of Canada Discovery (DLM, TDS, WSM) and Collaborative Research and Development Programs (DLM); NOAA/National Sea Grant NA86RG0052 (LJB), NA16RG2273 (SIK, MEH,GVC, JJS); Environmental Protection Agency U91620701 (WSB), R82902201(SC) and EPAâs Office of Research and Development (DEN)
Transnasal Sphenopalatine Ganglion Block for the Preventive Treatment of Chronic Daily Headache in Adolescents
Chronic headaches are a major source of morbidity in the pediatric population, affecting physical function, school attendance, social capacity, mood, and sleep. In adults, repetitive sphenopalatine ganglion (SPG) blockade has been studied as a preventive treatment for chronic migraines. This case series aims to evaluate the SPG block for the preventive treatment of chronic daily headache (CDH) in adolescents. We prospectively evaluated 17 adolescents (14 females, 14 ± 1 year) with CDH not responding to cognitive behavioral therapy (CBT), physiotherapy, and standard medications. Each patient received 10 SPG blocks (two blocks/week) using the Tx360Âź device. At the end of treatment, 10 patients (59%) reported a Patientâs Global Impression of Change (PGIC) score â„ 67%, and 3 months after the end of treatment, nine patients (53%) sustained a PGIC â„ 67%. There was also a statistically significant reduction in the depression subscale of the Revised Childrenâs Anxiety and Depression Scale (RCADS) at the end of treatment and 3 months post-treatment compared with baseline. The procedure was well tolerated with no adverse effects. In our study, the use of repeat SPG blockade was associated with sustained benefits on the PGIC and the depression subscale of the RCADS when used as preventive headache treatment in adolescents with refractory CDH
Hypnosis and cognitive behavioral therapy with online sessions to reduce fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer: Rational and study protocol for a feasibility study
International audienc
Hypnosis and cognitive behavioral therapy with online sessions to reduce fatigue in patients undergoing chemotherapy for a metastatic colorectal cancer: Rational and study protocol for a feasibility study
International audienc
<scp>RIPK3</scp> dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease
International audienceBackground and aims: Receptor-interacting protein kinase 3 (RIPK3) mediates NAFLD progression, but its metabolic function is unclear. Here, we aimed to investigate the role of RIPK3 in modulating mitochondria function, coupled with lipid droplet (LD) architecture in NAFLD.Approach and results: Functional studies evaluating mitochondria and LD biology were performed in wild-type (WT) and Ripk3-/- mice fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks and in CRISPR-Cas9 Ripk3-null fat-loaded immortalized hepatocytes. The association between hepatic perilipin (PLIN) 1 and 5, RIPK3, and disease severity was also addressed in a cohort of patients with NAFLD and in PLIN1-associated familial partial lipodystrophy. Ripk3 deficiency rescued impairment in mitochondrial biogenesis, bioenergetics, and function in CDAA diet-fed mice and fat-loaded hepatocytes. Ripk3 deficiency was accompanied by a strong upregulation of antioxidant systems, leading to diminished oxidative stress upon fat loading both in vivo and in vitro. Strikingly, Ripk3-/- hepatocytes displayed smaller size LD in higher numbers than WT cells after incubation with free fatty acids. Ripk3 deficiency upregulated adipocyte and hepatic levels of LD-associated proteins PLIN1 and PLIN5. PLIN1 upregulation controlled LD structure and diminished mitochondrial stress upon free fatty acid overload in Ripk3-/- hepatocytes and was associated with diminished human NAFLD severity. Conversely, a pathogenic PLIN1 frameshift variant was associated with NAFLD and fibrosis, as well as with increased hepatic RIPK3 levels in familial partial lipodystrophy.Conclusions: Ripk3 deficiency restores mitochondria bioenergetics and impacts LD dynamics. RIPK3 inhibition is promising in ameliorating NAFLD
RIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease
Background and Aims: Receptorâinteracting protein kinase 3 (RIPK3)
mediates NAFLD progression, but its metabolic function is unclear. Here, we
aimed to investigate the role of RIPK3 in modulating mitochondria function,
coupled with lipid droplet (LD) architecture in NAFLD.
Approach and Results: Functional studies evaluating mitochondria and LD
biology were performed in wildâtype (WT) and Ripk3â/â mice fed a cholinedeficient,
amino acidâdefined (CDAA) diet for 32 and 66 weeks and in
CRISPRâCas9 Ripk3ânull fatâloaded immortalized hepatocytes. The association
between hepatic perilipin (PLIN) 1 and 5, RIPK3, and disease severity
was also addressed in a cohort of patients with NAFLD and in PLIN1â
associated familial partial lipodystrophy. Ripk3 deficiency rescued impairment
in mitochondrial biogenesis, bioenergetics, and function in CDAA dietâ
fed mice and fatâloaded hepatocytes. Ripk3 deficiency was accompanied by
a strong upregulation of antioxidant systems, leading to diminished oxidative
stress upon fat loading both in vivo and in vitro. Strikingly, Ripk3â/â hepatocytes
displayed smaller size LD in higher numbers than WT cells after
incubation with free fatty acids. Ripk3 deficiency upregulated adipocyte and
hepatic levels of LDâassociated proteins PLIN1 and PLIN5. PLIN1 upregulation
controlled LD structure and diminished mitochondrial stress upon free
fatty acid overload in Ripk3â/â hepatocytes and was associated with diminished
human NAFLD severity. Conversely, a pathogenic PLIN1 frameshift
variant was associated with NAFLD and fibrosis, as well as with increased
hepatic RIPK3 levels in familial partial lipodystrophy.
Conclusions: Ripk3 deficiency restores mitochondria bioenergetics and
impacts LD dynamics. RIPK3 inhibition is promising in ameliorating NAFLD
Le Clown
Figure emblĂ©matique, mythique, universelle des arts du spectacle dans ce second millĂ©naire finissant, le clown nâen finit pas de porter beau. Il inflĂ©chit le discours de la dĂ©rision dans les domaines les plus variĂ©s de la tradition comme de la modernitĂ©. Investissant lâunivers du social et du politique, il se dĂ©cline de plus en plus souvent au fĂ©minin. Si le clown habite la conscience du citoyen, sâil contribue Ă la mise Ă distance de la vie quotidienne, il permet aussi la relecture du patrimoine culturel international. Le clown dĂ©stabilise pour mieux cimenter les humains par le rire. Sâil dĂ©sacralise, câest pour mieux permettre de structurer, dâaffirmer prioritĂ©s, valeurs individuelles et communautaires