Adipose tissue macrophage (ATM) has been shown to play a key role in the pathogenesis of obesity-associated adipose tissue inflammation and metabolic diseases. However, the upstream factors that integrate the environmental signals to control ATM activation and adipose inflammation in obesity remain elusive. Here, we identify BAF60a, a subunit of the SWI/SNF chromatin remodeling complexes, as the central checkpoint regulator of obesity-induced ATM activation, adipose tissue inflammation and systemic metabolic impairment. BAF60a expression was robustly downregulated in the adipose tissue stromal vascular fractions (SVFs) in type 2 diabetic mice. Myeloid-specific BAF60a ablation (BaMKO) promotes ATM pro-inflammatory activation, exacerbating diet-induced obesity, insulin resistance and metabolic dysfunction. Conversely, myeloid-specific overexpression of BAF60a in mice attenuates macrophage pro-inflammatory activation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate that BAF60a inactivation triggers the expression of pro-inflammatory gene program through chromatin remodeling. Moreover, motif analysis of ATAC-Seq and CUT&Tag-Seq data identifies the transcription factor Atf3 that physically interacts with BAF60a to suppress the pro-inflammatory gene expression, thereby controlling ATM activation and metabolic inflammation in obesity. Consistently, myeloid-specific Atf3 deficiency also promotes the pro-inflammatory activation of macrophage. Together, this work uncovers BAF60a/Atf3 axis as the key regulator in obesity-associated ATM activation, adipose tissue inflammation and metabolic diseases.

Pancreatic β-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes (T2D). Recent clinical and experimental studies have suggested that the functional capacity of β-cells, particularly in the first phase of insulin secretion, is a primary contributor to the progression of T2D and its associated complications. Pancreatic β-cells undergo dynamic compensation and decompensation processes during the development of T2D, in which metabolic stresses such as endoplasmic reticulum (ER) stress, oxidative stress, and inflammatory signals are key regulators of β-cell dynamics. Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D, especially in the early stages. Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague, accumulating evidence has implicated the improvement of β-cell functional capacity. In this review, we summarize recent advances in the understanding of the dynamic adaptations of β-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions on β-cell dysfunction in T2D. This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D, and more importantly, it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.

The overvoltage during hard switching limits the full utilization of devices due to higher blocking voltage requirement. The faster switching speed of SiC MOSFET worsens the trade-off, and the understanding of the overvoltage’s mechanism is crucial for the better utilization. In this paper, experimental characterizations on the influence of circuit parasitic parameters and gate resistances on overvoltage are performed. Furthermore, a SPICE-based device behavioral model is built and found to able to accurately predict the overvoltage. The same method could be applied to device rating selection in converter design.