Estrogen counteracts age-related decline in beige adipogenesis through the NAMPT-regulated ER stress response.

Thermogenic beige adipocytes are recognized as potential therapeutic targets for combating metabolic diseases. However, the metabolic advantages that they offer are compromised with aging. Here we show that treating mice with estrogen (E2), a hormone that decreases with age, can counteract the age-related decline in beige adipogenesis when exposed to cold temperature while concurrently enhancing energy expenditure and improving glucose tolerance in mice. Mechanistically, we found that nicotinamide phosphoribosyl transferase (NAMPT) plays a pivotal role in facilitating the formation of E2-induced beige adipocytes, which subsequently suppresses the onset of age-related endoplasmic reticulum (ER) stress. Furthermore, we found that targeting NAMPT signaling, either genetically or pharmacologically, can restore the formation of beige adipocytes by increasing the number of perivascular adipocyte progenitor cells. Conversely, the absence of NAMPT signaling prevents this process. Together, our findings shed light on the mechanisms regulating the age-dependent impairment of beige adipocyte formation and underscore the E2-NAMPT-controlled ER stress pathway as a key regulator of this process.

Estrogen prevents age-dependent beige adipogenesis failure through NAMPT-controlled ER stress pathway.

Thermogenic beige adipocytes are recognized as potential therapeutic targets for combating metabolic diseases. However, the metabolic advantages they offer are compromised with aging. Here, we show that treating mice with estrogen (E2), a hormone that decreases with age, to mice can counteract the aging- related decline in beige adipocyte formation when subjected to cold, while concurrently enhancing energy expenditure and improving glucose tolerance. Mechanistically, we find that nicotinamide phosphoribosyltranferase (NAMPT) plays a pivotal role in facilitating the formation of E2-induced beige adipocytes, which subsequently suppresses the onset of age-related ER stress. Furthermore, we found that targeting NAMPT signaling, either genetically or pharmacologically, can restore the formation of beige adipocytes by increasing the number of perivascular adipocyte progenitor cells. Conversely, the absence of NAMPT signaling prevents this process. In conclusion, our findings shed light on the mechanisms governing the age-dependent impairment of beige adipocyte formation and underscore the E2-NAMPT controlled ER stress as a key regulator of this process. Highlights: Estrogen restores beige adipocyte failure along with improved energy metabolism in old mice.Estrogen enhances the thermogenic gene program by mitigating age-induced ER stress.Estrogen enhances the beige adipogenesis derived from SMA+ APCs.Inhibiting the NAMPT signaling pathway abolishes estrogen-promoted beige adipogenesis.

Empagliflozin inhibits angiotensin II-induced hypertrophy in H9c2 cardiomyoblasts through inhibition of NHE1 expression.

Diabetes mellitus (DM)-induced cardiac morbidities have been the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors including empagliflozin (EMPA), which have been approved for the treatment of DM, have gained attention for their cardioprotective effect. The mechanism by which SGLT-2 inhibitors exert their cardioprotective effect remains unclear. Recent studies have suggested that EMPA exerts its cardioprotective effect by inhibiting the Na+/H+ exchanger (NHE), a group of membrane proteins that regulate intracellular pH and cell volume. Increased activity and expression of NHE isoform 1 (NHE1), the predominant isoform expressed in the heart, leads to cardiac hypertrophy. p90 ribosomal s6 kinase (p90 RSK) has been demonstrated to stimulate NHE1 activity. In our study, H9c2 cardiomyoblasts were treated with angiotensin II (ANG) to activate NHE1 and generate a hypertrophic model. We aimed to understand whether EMPA reverses the ANG-induced hypertrophic response and to elucidate the molecular pathway contributing to the cardioprotective effect of EMPA. Our study demonstrated that ANG-induced hypertrophy of H9c2 cardiomyoblasts is accompanied with increased SGLT-1 and NHE1 protein expression, an effect which is prevented in the presence of EMPA. EMPA reduces ANG-induced hypertrophy through the inhibition of SGLT-1 and NHE1 expression.

National assessment of pharmaceutical workforce and education using the International Pharmaceutical Federation's global development goals: a case study of Qatar.

BACKGROUND: The sustainable development goals were launched by the United Nations in 2015. Its fifth goal was describing the achievement of universal health coverage by 2030. This goal reaffirms the importance of investing in the development and training of the global health workforce. In alliance with this, the International Pharmaceutical Federation (FIP) has published reports about pharmacy workforce planning in several countries. However, data about Qatar were not included in these reports. In 2017, FIP developed a transformational roadmap of pharmaceutical workforce and education. One systematic framework component of the roadmap is the Pharmaceutical Workforce Development Goals (DG[w]s) that were released in late 2016 and subsequently incorporated into the more comprehensive Global Development Goals1 in 2020, encompassing not only workforce development, but additionally practice and pharmaceutical science development. This study aimed to evaluate the current situation of pharmacy workforce and education in Qatar in relation to the original 13 Pharmaceutical Workforce Development Goals (DG[w]s). The objective was to identify the gaps in pharmacy workforce and education and to recommend evidence-led strategies to be included in both the Ministry of Public Health and the Qatar University College of Pharmacy workforce development plans. METHODS: Three rounds of conventional Delphi technique were conducted with expert panels of key decision-makers in pharmacy practice from the College of Pharmacy at Qatar University and the Ministry of Public Health, utilizing the FIP's self-assessment survey. Qualitative content analysis was used to analyze and prioritize the identified gaps from the collected data. DG[w] was considered "met" if all the provided indicators were achieved, "partially met" if at least one of the indicators were achieved, and "not met" if none of the indicators were achieved RESULTS: The lack of competency framework (DG[w]5), workforce data (DG[w]12), and workforce policy formation (DG[w]13) are three major gaps in the provision of pharmaceutical workforce and pharmacy education in Qatar, influencing other DG[w]s. These gaps need to be addressed by the formation of Qatar Pharmaceutical Association through which academic, practice, and policymaking sectors can work together in developing health workforce intelligence system. CONCLUSION: The results indicated that DG[w]s are interrelated and a gap in one goal can negatively influence others. Results and recommendations of this research will facilitate the implementation of strategic plans across leading pharmacy sectors to meet health needs in Qatar and achieve the third pillar of the Qatar National Vision 2030.