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.

Revisited guidelines for metabolic tolerance tests in mice.

Preclinical mouse models are extensively used in biomedical research to gain insight into disease mechanisms and to test new drug treatments. Glucose and insulin tolerance tests are simple experimental tests frequently used worldwide to assess glucose metabolism in mice. Various guidelines and methodological considerations have been published to help researchers standardize procedures and optimize research outcomes.

The impact of new onset diabetes on cardiovascular risks in orthotopic liver transplant recipients: findings from the COLT study.

Background: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).

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.

Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve individuals according to diabetes duration: Results from the REALI European pooled data analysis.

Aim: To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD).

Materials And Methods: We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks.

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.

Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism.

Background: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.

Objective: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.

Design: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).

Obesity alters adipose tissue response to fasting and refeeding in women: A study on lipolytic and endocrine dynamics and acute insulin resistance.

Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period.

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.

IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.

While mechanisms controlling uncoupling protein-1 (UCP1) in thermogenic adipocytes play a pivotal role in non-shivering thermogenesis, it remains unclear whether FFo-ATP synthase function is also regulated in brown adipose tissue (BAT). Here, we show that inhibitory factor 1 (IF1, encoded by Atp5if1), an inhibitor of ATP synthase hydrolytic activity, is a critical negative regulator of brown adipocyte energy metabolism. In vivo, IF1 levels are diminished in BAT of cold-adapted mice compared to controls.

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.

From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.

2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It is synthesized on demand in postsynaptic membranes through the sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) and diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations of PLC and DAGL isoforms, as well as additional intracellular pathways implying other enzymes and substrates.

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.

GDF15 is dispensable for the insulin-sensitizing effects of chronic exercise.

Growth and differentiation factor 15 (GDF15) has recently emerged as a weight loss and insulin-sensitizing factor. Growing evidence also supports a role for GDF15 as a physiological, exercise-induced stress signal. Here, we tested whether GDF15 is required for the insulin-sensitizing effects of exercise in mice and humans.

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.