Estrogen receptor α controls metabolism in white and brown adipocytes by regulating Polg1 and mitochondrial remodeling.

Obesity is heightened during aging, and although the estrogen receptor α (ERα) has been implicated in the prevention of obesity, its molecular actions in adipocytes remain inadequately understood. Here, we show that adipose tissue ESR1/Esr1 expression inversely associated with adiposity and positively associated with genes involved in mitochondrial metabolism and markers of metabolic health in 700 Finnish men and 100 strains of inbred mice from the UCLA Hybrid Mouse Diversity Panel. To determine the anti-obesity actions of ERα in fat, we selectively deleted Esr1 from white and brown adipocytes in mice. In white adipose tissue, Esr1 controlled oxidative metabolism by restraining the targeted elimination of mitochondria via the E3 ubiquitin ligase parkin. mtDNA content was elevated, and adipose tissue mass was reduced in adipose-selective parkin knockout mice. In brown fat centrally involved in body temperature maintenance, Esr1 was requisite for both mitochondrial remodeling by dynamin-related protein 1 (Drp1) and uncoupled respiration thermogenesis by uncoupled protein 1 (Ucp1). In both white and brown fat of female mice and adipocytes in culture, mitochondrial dysfunction in the context of Esr1 deletion was paralleled by a reduction in the expression of the mtDNA polymerase γ subunit Polg1 We identified Polg1 as an ERα target gene by showing that ERα binds the Polg1 promoter to control its expression in 3T3L1 adipocytes. These findings support strategies leveraging ERα action on mitochondrial function in adipocytes to combat obesity and metabolic dysfunction.

National Analysis of Risk Factors for Nasal Fractures and Associated Injuries in Trauma.

Nasal fractures account for up to 58% of facial fractures. However, the literature characterizing associated injuries and risk factors for nasal fractures is sparse and is mostly composed of single-center experiences. This study sought to provide a large descriptive analysis and identify associated injuries and risk factors for nasal fractures in trauma using a national database. A retrospective analysis of the National Trauma Data Bank (NTDB) from 2007 to 2015 was performed. Patients ≥18 years of age with nasal fractures were included. A multivariable logistic regression model was used to identify predictors for nasal fracture in trauma. Of 5,494,609 trauma patients in the NTDB, 255,533 (4.6%) had a nasal fracture. Most were male (74.8%) with a mean age of 45.6 years. Blunt trauma accounted for 90.5% of fractures, with motor vehicle accident being the most common mechanism (27.5%). Closed fractures occurred in 93.0% of patients. Concomitant injuries included traumatic brain injury (TBI; 56.9%), malar/maxillary fracture (27.9%), and open wound of the face (38.6%) and nose (9.5%). Of all patients, 10.1% underwent closed or open reductions at index hospitalization. The strongest associated injuries with nasal fracture included open wound of the nose (odds ratio [OR]: 8.71, 95% confidence interval [CI]: 8.49-8.94, p < 0.001), epistaxis (OR: 5.26, 95% CI: 4.59-6.02, p < 0.001), malar/maxillary fracture (OR: 4.38, 95% CI: 4.30-4.45, p < 0.001), and orbital fracture (OR: 3.99, 95% CI: 3.91-4.06, p < 0.001). Nasal fractures are common traumatic injuries with more than 90% occurring by blunt mechanism and over half suffering from a concomitant TBI. The strongest associated injury with nasal fracture is an open wound of the nose.

RNA-binding protein ZFP36L1 maintains posttranscriptional regulation of bile acid metabolism.

Bile acids function not only as detergents that facilitate lipid absorption but also as signaling molecules that activate the nuclear receptor farnesoid X receptor (FXR). FXR agonists are currently being evaluated as therapeutic agents for a number of hepatic diseases due to their lipid-lowering and antiinflammatory properties. FXR is also essential for maintaining bile acid homeostasis and prevents the accumulation of bile acids. Elevated bile acids activate FXR, which in turn switches off bile acid synthesis by reducing the mRNA levels of bile acid synthesis genes, including cholesterol 7α-hydroxylase (Cyp7a1). Here, we show that FXR activation triggers a rapid posttranscriptional mechanism to degrade Cyp7a1 mRNA. We identified the RNA-binding protein Zfp36l1 as an FXR target gene and determined that gain and loss of function of ZFP36L1 reciprocally regulate Cyp7a1 mRNA and bile acid levels in vivo. Moreover, we found that mice lacking hepatic ZFP36L1 were protected from diet-induced obesity and steatosis. The reduced adiposity and antisteatotic effects observed in ZFP36L1-deficient mice were accompanied by impaired lipid absorption that was consistent with altered bile acid metabolism. Thus, the ZFP36L1-dependent regulation of bile acid metabolism is an important metabolic contributor to obesity and hepatosteatosis.