Inflammation hasto fight pathogens fast—but it can't get out of control. Researchers at the German Cancer Research Center (DKFZ) have now deciphered in more detail how the organism masters this balancing act. Their work shows that cells use two different strategies to precisely control inflammatory genes and thus precisely regulate the inflammatory response.

Beige fat surrounding blood vessels actively works to keep high blood pressure in check, according to a new study in mice, promoting healthy vascular function even during obesity. The findings support the notion that therapeutic activation of thermogenic fat tissue could help reduce the risk of cardiovascular disease. High blood pressure is a leading cause of heart disease and stroke and is a major risk factor for early death. Adipose tissue, or fat, plays an active role in regulating blood pressure. However, growing evidence suggests that it’s the type of fat, not simply the amount, that seems to matter most. While excess white fat is linked to higher blood pressure, brown and beige fat – best known for their role in producing metabolic heat – is associated with a lower risk of hypertension, even in obesity. Beige perivascular adipose tissue (PVAT) surrounds blood vessels and has features of both white and brown fat. Yet, despite these observations, it has been difficult to disentangle the specific roles of different fat types and determine the mechanisms linking adipose biology and blood pressure regulation.

 

Using mice genetically engineered to lack functional beige fat tissue, Masha Koenen and colleagues show that beige PVAT supports healthy blood vessels and blood pressure control. According to the findings, mice lacking the protein PRDM16 – a major gene expression regulator of the adipose beiging process – showed extensive remodeling of perivascular adipose tissue, increased vasoconstriction and vascular fibrosis, and increased blood pressure, even without obesity. Koenen et al. show that loss of Prdm16 depressed the circulating enzyme QSOX1 and that deleting Qsox1 in Prdm16-deficient mice prevented vascular fibrosis, normalized vascular function, and reduced blood pressure. Moreover, in a meta-analysis of genome-wide association studies that used data from three biobanks, the authors found that human PRDM16 variants were associated with higher blood pressure. “Koenen et al.’s findings suggest that the activation of brown adipose tissue by boosting or stabilizing PRDM16 expression could have cardiovascular benefits,” write Mandy Grootaert and Aernout Luttun in a related Perspective. “Although current human and nonhuman data are encouraging, well-controlled clinical trials are needed to determine whether triggering beiging of adipose tissue reduces the frequency of adverse cardiovascular events in patients.”

Even at amounts considered safe under regulatory frameworks, chronic exposure to the pesticide chlorpyrifos accelerates physiological aging and shortens the life spans of wild fish, according to a new study based in China. The findings raise concerns about the long-term impacts of low-level environmental pesticide contamination. Traditionally, to define risk, chemical safety regulations have relied on the acute dangers of short-term exposure to high doses. While this method captures immediate toxicity, it assumes that exposure to much lower concentrations is more or less harmless.  However, low concentrations of chemical pollutants, like pesticides, are widespread in the environment, and the effects of chronic low-dose exposure on animal life span in the wild are poorly understood. To assess how low-level pesticide exposure affects wild fish, Kai Huang combined field observations of 24,388 lake stargazer fish (Culter Dabryi) from lakes in China with persistent low levels of the common pesticide chlorpyrifos, with laboratory experiments involving exposing fish to controlled doses of this chemical over time. Huang et al. found that fish from pesticide-impacted lakes showed shortened telomeres; they also exhibited truncated population structures, dominated by younger individuals, suggesting that chronic, low-dose chlorpyrifos exposure is associated with accelerated physiological aging and shortened life spans. These findings were confirmed in laboratory experiments that revealed chronic low-dose exposure reduced fish survival and degraded telomeres in a dose- and physiological age-dependent manner – effects which were not seen with acute high-dose exposure. “Given the conserved mechanisms of telomere biology across vertebrates, chronic low-dose exposure to these chemicals may pose similar aging-related risks in humans, potentially contributing to age-associated diseases,” Huang et al. write.

The European Molecular Biology Laboratory (EMBL) and the Institute for Bioengineering of Catalonia (IBEC) aim to contribute to the discussion on challenges and opportunities in the expanding field of engineered multicellular systems.