Videos
Maternal obesity has been associated with adverse outcomes in offspring; however, it is not clear how maternal obesity or high-fat diet (HFD) impart long-term effects on offspring. In this episode, Julie Mirpuri and colleagues use murine models to evaluate the effects of HFD during pregnancy on offspring. The offspring of HFD-fed mothers developed a microbiome that was distinctly different than that of offspring of mothers on a regular diet. Moreover, IL-17–producing type 3 innate lymphoid cells (ILC3s) were increased the offspring of HFD-fed mothers, a phenotype linked to the HFD-associated microbiota. The offspring of HFD-fed mothers were also more susceptible to necrotizing enterocolitis. Together, these results indicate that maternal HFD influences the offspring microbiome, thereby increasing ILC3s and susceptibility to inflammatory insult.
The proinflammatory adipokine lipocalin-2 is upregulated in obese individuals and is thought to drive renal injuries; however, the source of lipocalin-2 during kidney dysfunction is not fully understood. In this episode, Wai Yan Sun, Bo Bai, and colleagues used multiple murine models of chronic and acute kidney injury to evaluate the role of lipocalin-2. Adipose-tissue-specific deletion, but not whole-body or kidney-specific deletion, of lipocalin-2 protected mice from aldosterone- and high salt after uninephrectomy-induced kidney damage. Moreover, transplantation of WT fat pads into animals with lipocalin-2 deficient adipose tissue restored sensitivity to renal damage, and mice chronically exposed to a stable variant of human lipocalin-2 developed renal injury. Together, these results identify adipose-generated lipocalin-2 as a driver of acute and chronic kidney dysfunction.
Adult polyglucosan body disease (APBD) is a glycogen storage disorder characterized by the accumulation of polyglucosan bodies in muscle, nerve, and other tissue as the result of mutations in glycogen branching enzyme 1 (GBE1). APBD is characterized by adult-onset neurodegeneration, and recent evidence suggests that reduction of glucose 6-phosphate–stimulated glycogen synthase (GYS) activity may be beneficial. In this episode, Or Kakhlon and colleagues screened FDA-approved compounds for those able to reduce GYS activity and polyglucosan accumulation in APBD fibroblasts. Guaiacol emerged as a potential candidate from this screen and improved grip strength and increased lifespan in murine APBD models. These improvements corresponded with reduced polyglucosans in peripheral nerves, liver and heart. Together, these results support further exploration of guaiacol for treating APBD.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive pulmonary fibrosis and eventual loss of function. The transcription factor Wilms’ tumor 1 (WT1) promotes cell proliferation and is critical for lung development. This factor has been shown to be upregulated in IPF; however, the role of WT1 in IPF development is not fully understood. In this episode, Satish Madala and colleagues used lineage tracing to show that WT1 promotes fibroblast activation, fibroproliferation, myofibroblast transformation, and ECM production in a murine model of IPF. Moreover, partial loss of WT1 reduced fibrotic phenotypes. Together, these results identify WT1 as an important driver of lung fibrosis and support further exploration of WT1 as a therapeutic target.
White adipose tissue (WAT) serves primarily as energy storage; however, in response to cold or β-adrenergic agonists, WAT develops characteristics of brown adipose tissue (BAT), which expends energy in the form of heat. WAT beiging has proposed as potential strategy for treating obesity. In this episode, Philip Kern and colleagues exposed lean and obese subjects to cold or treatment with the β3 agonist mirabegron and evaluated markers of adipose beiging. Both treatments induced beiging, regardless of obesity status or age. The results of this study support further evaluation of the long-term effects of induced adipose beiging for treatment of obesity and associated metabolic dysfunction.
