1.Surfactant protein A promotes western diet-induced hepatic steatosis and fibrosis in mice

DOI: 10.1038/s41598-024-58291-5

https://www.nature.com/articles/s41598-024-58291-5

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition in the US due to rising metabolic dysfunction and obesity rates. Despite its significance, the role of surfactant protein A (SPA) in MASLD remains unclear. Researchers induced MASLD in mice and found elevated SPA levels in affected livers. SPA deficiency led to reduced lipid accumulation, decreased inflammation, and inhibited liver fibrosis. Notably, SPA deficiency attenuated fatty acid uptake by hepatocytes, curbing excessive lipid buildup, inflammation, and fibrosis characteristic of MASLD. These findings unveil SPA's novel involvement in MASLD pathogenesis, suggesting it as a potential therapeutic target for combating this prevalent liver disease.

2.Risk factors for suboptimal glycemic control in pediatrics with type 1 diabetes mellitus: a cross-sectional study

DOI: 10.1038/s41598-024-57205-9

https://www.nature.com/articles/s41598-024-57205-9

This cross-sectional study aimed to assess factors influencing glycemic control in 204 pediatric patients with type 1 diabetes mellitus (T1DM). Patients aged 10-14 years and those with longer diabetes duration had higher odds of suboptimal glycemic control. Multivariable analysis confirmed the association, with patients aged 10-14 years showing a significant risk (adjusted odds ratio [AOR] 4.85). Additionally, a significant correlation existed between individuals with BMI ≥ 95th percentile and suboptimal glycemic control. These findings underscore the importance of age and obesity in predicting long-term glycemic control in pediatric T1DM patients, offering crucial insights for diagnosis and management strategies.

3.Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity

DOI: 10.1038/s41467-024-46009-0

https://www.nature.com/articles/s41467-024-46009-0

The study demonstrates that saturated fatty acids activate the NAD+ salvage pathway in hypothalamic astrocytes. Inhibiting this pathway reduces hypothalamic inflammation and curbs obesity development in male mice on a high-fat diet (HFD). CD38, downstream of the NAD+ salvage pathway, plays a role in hypothalamic astrocytes under fat overload. Activation of the NAMPT-NAD+-CD38 axis triggers proinflammatory responses in the hypothalamus, leading to dysfunctional astrocytes. This activation also disrupts basal Ca2+ signals and impairs responses to metabolic hormones like insulin, leptin, and glucagon-like peptide 1. The findings underscore the importance of the hypothalamic astrocytic NAD+ salvage pathway, alongside CD38, in HFD-induced obesity.

4.Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions

DOI: 10.1038/s41467-024-45995-5

https://www.nature.com/articles/s41467-024-45995-5

In obesity and breast cancer (BC), small extracellular vesicles (sEVs) play a crucial role in cargo transport. Obesity increases circulating sEV levels of extracellular matrix protein 1 (ECM1) via integrin-β2 dependence. Breast cancer cells overexpressing ECM1 exhibit elevated matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. sEVs from obese mice deliver more ECM1 to BC cells, enhancing cancer cell invasion and migration. Treatment with these sEVs promotes BC metastasis and growth in mouse models by increasing tumor levels of MMP3 and S100A/B. This study uncovers a mechanism linking obesity to BC progression via sEV-mediated ECM1 transfer and suggests sEV-based therapies for obesity-associated BC.

5.Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders

DOI: 10.1038/s41467-024-45568-6

https://www.nature.com/articles/s41467-024-45568-6

IL-22 plays a crucial role in mitigating obesity-induced metabolic disorders, but its specific tissue targets remain unclear. This study investigates tissue-specific IL-22RA1 signaling in long-term high-fat diet (HFD)-induced metabolic disorders. Intestinal epithelium and liver IL-22RA1 signaling improve systemic glucose metabolism, while intestinal signaling also affects liver and white adipose tissue (WAT) metabolism in a microbiota-dependent manner. The study identifies a link between Oscillibacter and WAT inflammation, regulated by IL-22 and potentially IL-22-induced IL-18. Paneth cell-specific IL-22RA1 signaling partly mediates systemic glucose metabolism post-HFD. These findings highlight the importance of intestinal epithelium-specific IL-22RA1 signaling in regulating intestinal metabolism and alleviating systemic obesity-related disorders.