Depletion of JunB increases adipocyte thermogenic capacity and ameliorates diet-induced insulin resistance.

The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. Here we show that in male mice, a population of transcription factor jun-B (JunB)-enriched (JunB+) adipocytes within the brown adipose tissue exhibits lower thermogenic capacity compared to high-thermogenic adipocytes. The JunB+ adipocyte population expands in obesity. Depletion of JunB in adipocytes increases the fraction of adipocytes exhibiting high thermogenic capacity, leading to enhanced basal and cold-induced energy expenditure and protection against diet-induced obesity and insulin resistance. Mechanistically, JunB antagonizes the stimulatory effects of PPARγ coactivator-1α on high-thermogenic adipocyte formation by directly binding to the promoter of oestrogen-related receptor alpha, a PPARγ coactivator-1α downstream effector. Taken together, our study uncovers that JunB shapes thermogenic adipocyte heterogeneity, serving a critical role in maintaining systemic metabolic health.

Emerging integrated SERS-microfluidic devices for analysis of cancer-derived small extracellular vesicles.

Cancer-derived small extracellular vesicles (sEVs) are specific subgroups of lipid bilayer vesicles secreted from cancer cells to the extracellular environment. They carry distinct biomolecules (e.g., proteins, lipids and nucleic acids) from their parent cancer cells. Therefore, the analysis of cancer-derived sEVs can provide valuable information for cancer diagnosis. However, the use of cancer-derived sEVs in clinics is still limited due to their small size, low amounts in circulating fluids, and heterogeneous molecular features, making their isolation and analysis challenging. Recently, microfluidic technology has gained great attention for its ability to isolate sEVs in minimal volume. In addition, microfluidics allows the isolation and detection of sEVs to be integrated into a single device, offering new opportunities for clinical application. Among various detection techniques, surface-enhanced Raman scattering (SERS) has emerged as a promising candidate for integrating with microfluidic devices due to its ultra-sensitivity, stability, rapid readout, and multiplexing capability. In this tutorial review, we start with the design of microfluidics devices for isolation of sEVs and introduce the key factors to be considered for the design, and then discuss the integration of SERS and microfluidic devices by providing descriptive examples of the currently developed platforms. Lastly, we discuss the current limitations and provide our insights for utilising integrated SERS-microfluidics to isolate and analyse cancer-derived sEVs in clinical settings.

COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity.

Cyclooxygenase-2 (COX-2) plays a critical role in regulating innate immunity and metabolism by producing prostaglandins (PGs) and other lipid mediators. However, the implication of adipose COX-2 in obesity remains largely unknown. Using adipocyte-specific COX-2 knockout (KO) mice, we showed that depleting COX-2 in adipocytes promoted white adipose tissue development accompanied with increased size and number of adipocytes and predisposed diet-induced adiposity, obesity, and insulin resistance. The increased size and number of adipocytes by COX-2 KO were reversed by the treatment of prostaglandin E2 (PGE2) but not PGI2 and PGD2 during adipocyte differentiation. PGE2 suppresses PPARγ expression through the PKA pathway at the early phase of adipogenesis, and treatment of PGE2 or PKA activator isoproterenol diminished the increased lipid droplets in size and number in COX-2 KO primary adipocytes. Administration of PGE2 attenuated increased fat mass and fat percentage in COX-2 deficient mice. Taken together, our study demonstrated the suppressing effect of adipocyte COX-2 on adipogenesis and reveals that COX-2 restrains adipose tissue expansion via the PGE2-mediated paracrine mechanism and prevents the development of obesity and related metabolic disorders.