Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.

Mice with genetic ablation of PI3Kγ are protected from diet-induced obesity. However, the cell type responsible for PI3Kγ action in obesity remains unknown. We generated mice with conditional deletion of PI3Kγ in neurons using the nestin promoter to drive the expression of the Cre recombinase (PI3Kγ mice) and investigated their metabolic phenotype in a model of diet-induced obesity.

Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging.

Biological age, which reflects the physiological state of an individual, offers a better predictive value than chronological age for age-related diseases and mortality. Nonetheless, determining accurate functional features of biological age remains challenging due to the multifactorial nature of aging. Here, we established a unique mouse cohort comprising 1576 male and female outbred SWISS mice subjected or not to high-fat, high-sucrose diet to investigate multiorgan/system biological aging throughout adulthood.

Lipid sensing by PPARα: Role in controlling hepatocyte gene regulatory networks and the metabolic response to fasting.

Peroxisome proliferator-activated receptors (PPARs) constitute a small family of three nuclear receptors that act as lipid sensors, and thereby regulate the transcription of genes having key roles in hepatic and whole-body energy homeostasis, and in other processes (e.g., inflammation), which have far-reaching health consequences.

Ventilation strategies in cardiogenic shock: insights from the FRENSHOCK observational registry.

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely suggested as first-line ventilatory support in cardiogenic shock (CS) patients. We assessed the real-life use of different ventilation strategies in CS and their influence on short and mid-term prognosis.

Methods: FRENSHOCK was a prospective registry including 772 CS patients from 49 centers in France.

Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.

Estrogens act through nuclear and membrane-initiated signaling. Estrogen receptor alpha (ERα) is critical for reproduction, but the relative contribution of its nuclear and membrane signaling to the central regulation of reproduction is unclear. To address this question, two complementary approaches were used: estetrol (E) a natural estrogen acting as an agonist of nuclear ERs, but as an antagonist of their membrane fraction, and the C451A-ERα mouse lacking mERα.

The adipocyte apolipoprotein M is negatively associated with inflammation.

Obesity is associated with the development of local adipose tissue (AT) and systemic inflammation. Most adipokines are upregulated with obesity and have pro-inflammatory properties. Few are downregulated and possess beneficial anti-inflammatory effects.

Management of cardiogenic shock: state-of-the-art.

The management of cardiogenic shock is an ongoing challenge. Despite all efforts and tremendous use of resources, mortality remains high. Whilst reversing the underlying cause, restoring/maintaining organ perfusion and function are cornerstones of management.

[Novelties for the management of cytomegalovirus after kidney transplantation].

Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.

Simultaneous combined transplantation: Intricacies in immunosuppression management.

Simultaneous combined transplantation (SCT), i.e. the transplantation of two solid organs within the same procedure, can be required when the patients develop more than one end-stage organ failure.

Cardiogenic shock and infection: A lethal combination.

Background: Cardiogenic shock and sepsis are severe haemodynamic states that are frequently present concomitantly, leading to substantial mortality. Despite its frequency and clinical significance, there is a striking lack of literature on the outcomes of combined sepsis and cardiogenic shock.

Methods: FRENSHOCK was a prospective registry including 772 patients with cardiogenic shock from 49 centres.

Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism.

Background: Estrogen secretion by the ovaries regulates the hypothalamic-pituitary-gonadal axis during the reproductive cycle, influencing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion, and also plays a role in regulating metabolism. Here, we establish that hypothalamic tanycytes-specialized glia lining the floor and walls of the third ventricle-integrate estrogenic feedback signals from the gonads and couple reproduction with metabolism by relaying this information to orexigenic neuropeptide Y (NPY) neurons.

Methods: Using mouse models, including mice floxed for Esr1 (encoding estrogen receptor alpha, ERα) and those with Cre-dependent expression of designer receptors exclusively activated by designer drugs (DREADDs), along with viral-mediated, pharmacological and indirect calorimetric approaches, we evaluated the role of tanycytes and tanycytic estrogen signaling in pulsatile LH secretion, cFos expression in NPY neurons, estrous cyclicity, body-weight changes and metabolic parameters in adult females.

The admission level of CRP during cardiogenic shock is a strong independent risk marker of mortality.

Inflammatory processes are involved not only in coronary artery disease but also in heart failure (HF). Cardiogenic shock (CS) and septic shock are classically distinct although intricate relationships are frequent in daily practice. The impact of admission inflammation in patients with CS is largely unknown.

A minor tweak in transplant surgery protocols alters the cellular landscape of the arterial wall during transplant vasculopathy.

Introduction: Transplant vasculopathy (TV) is a major complication after solid organ transplantation, distinguished by an arterial intimal thickening that obstructs the vascular lumen and leads to organ rejection. To date, TV remains largely untreatable, mainly because the processes involved in its development remain unclear. Aortic transplantation in mice, used to mimic TV, relies on highly variable experimental protocols, particularly regarding the type of anastomosis used to connect the donor aorta to the recipient.

MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion.

Myogenesis is a multistep process that requires a spatiotemporal regulation of cell events resulting finally in myoblast fusion into multinucleated myotubes. Most major insights into the mechanisms underlying fusion seem to be conserved from insects to mammals and include the formation of podosome-like protrusions (PLPs) that exert a driving force toward the founder cell. However, the machinery that governs this process remains poorly understood.

Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart.

The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers.

Zinc unbound concentration as an anchor to drive individualize repletion.

Background And Aims: Zinc (Zn) quantification is of particular interest in many clinical condition (e.g. inflammatory disease, critical care).

P2Y13 receptor deficiency favors adipose tissue lipolysis and worsens insulin resistance and fatty liver disease.

Excessive lipolysis in white adipose tissue (WAT) leads to insulin resistance (IR) and ectopic fat accumulation in insulin-sensitive tissues. However, the impact of Gi-coupled receptors in restraining adipocyte lipolysis through inhibition of cAMP production remained poorly elucidated. Given that the Gi-coupled P2Y13 receptor (P2Y13-R) is a purinergic receptor expressed in WAT, we investigated its role in adipocyte lipolysis and its effect on IR and metabolic dysfunction-associated steatotic liver disease (MASLD).

Role of Perilipins in Oxidative Stress-Implications for Cardiovascular Disease.

Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and antioxidants in a cell. In the heart, oxidative stress may deteriorate calcium handling, cause arrhythmia, and enhance maladaptive cardiac remodeling by the induction of hypertrophic and apoptotic signaling pathways. Consequently, dysregulated ROS production and oxidative stress have been implicated in numerous cardiac diseases, including heart failure, cardiac ischemia-reperfusion injury, cardiac hypertrophy, and diabetic cardiomyopathy.

Optimal Heart Failure Medical Therapy and Mortality in Survivors of Cardiogenic Shock: Insights From the FRENSHOCK Registry.

Background: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS.

Methods And Results: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units.

[Teeth and oral cavity at the heart of systemic health].

Research into the interrelationships between oral and systemic diseases has been growing exponentially for over 20 years. Teeth and their supporting tissues can be affected by pathologies, particularly infectious ones, the consequences of which are felt locally in the oral cavity and at a distance in the body. Oral diseases frequently lead to the maintenance of an inflammatory state in oral bones and mucosa, which complicates the treatment of systemic inflammatory pathologies.

Ryanodine receptor dysfunction causes senescence and fibrosis in Duchenne dilated cardiomyopathy.

Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle weakness due to the absence of functional dystrophin. DMD patients also develop dilated cardiomyopathy (DCM). We have previously shown that DMD (mdx) mice and a canine DMD model (GRMD) exhibit abnormal intracellular calcium (Ca) cycling related to early-stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) contributing to age-dependent DCM.