Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
BACKGROUND: Addressing vulnerability to heat-related mortality is a necessary step in the development of policies dictated by heat action plans. We aimed to provide a systematic assessment of the epidemiologic evidence regarding vulnerability to heat-related mortality. METHODS: Studies assessing the association between high ambient temperature or heat waves and mortality among different subgroups and published between January 1980 and August 2014 were selected. Estimates of association for all the included subgroups were extracted. We assessed the presence of heterogeneous effects between subgroups conducting Cochran Q tests. We conducted random effect meta-analyses of ratios of relative risks (RRR) for high ambient temperature studies. We performed random effects meta-regression analyses to investigate factors associated with the magnitude of the RRR. RESULTS: Sixty-one studies were included. Using the Cochran Q test, we consistently found evidence of vulnerability for the elderly ages extgreater85 years. We found a pooled RRR of 0.99 (95% confidence interval [CI] = 0.97, 1.01) for male sex, 1.02 (95% CI = 1.01, 1.03) for age extgreater65 years, 1.04 (95% CI = 1.02, 1.07) for age extgreater75 years, 1.03 (95% CI = 1.01, 1.05) for low individual socioeconomic status (SES), and 1.01 (95% CI = 0.99, 1.02) for low ecologic SES. CONCLUSIONS: We found strongest evidence of heat-related vulnerability for the elderly ages extgreater65 and extgreater75 years and low SES groups (at the individual level). Studies are needed to clarify if other subgroups (e.g., children, people living alone) are also vulnerable to heat to inform public health programs
ISSN: 1044-3983

hal-01197347
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197347/file/Vulnerability%20to%20Heat-related%20Mortality%20A%20Systematic%20Review%2C%20Meta-analysis%2C%20and%20Meta-regression%20Analysis..pdf
DOI : 10.1097/EDE.0000000000000375

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
ISSN: 0021-9258

hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/file/JBC-2013-525220v2-Kristiansen-POSTPRINT.pdf
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Hepatocyte death is a central event during liver disease progression, in which immune cells play key roles by activating members of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), including TNFR1 (TNFRSF1A), Fas (TNFRSF6) and TRAIL-R2 (TNFRSF10B). Receptor Interacting Protein Kinase 1 (RIPK1) emerged as a signaling node downstream of these receptors. In the case of TNFR1, RIPK1 has been demonstrated to paradoxically serve as a scaffold to promote the survival of hepatocytes and as a kinase to kill them. To evaluate whether RIPK1 also protects hepatocytes from death in response to FasL or TRAIL, we took advantage of liver parenchymal cell-specific Ripk1 knockout mice (Ripk1 (LPC-KO)). We found that Ripk1 (LPC-KO) mice, as well as primary hepatocytes derived from them, were more susceptible to Fas-mediated apoptosis than their respective WT counterparts. Fas-induced hepatocyte death was independent of TNF-α signaling. Interestingly, while TRAIL administration did not induce hepatitis in Ripk1 (LPC-KO) mice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in the Ripk1 (LPC-KO) mice. Together, our data demonstrate the protective role of RIPK1 downstream of Fas and highlight the general protective function of RIPK1 in hepatocytes exposed to inflammatory conditions, where TNF-α, FasL and/or TRAIL are present.
ISSN: 2045-2322

hal-01579612
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579612
DOI : 10.1038/s41598-017-09789-8
PUBMED : 28835677