The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites.

一作：Bean, C., Audano,M., Varanita, T.，PI：Nico Mitro, LucaScorrano

发表单位：Department of Biology,University of Padova

Abstract

Peroxisomal β-oxidation acts as a sensor for intracellular fatty acids and regulates lipolysis

一作：Lianggong Ding，PI：Markus Heim ,ChristianWolfrum

发表单位：Institute of Food,Nutrition and Health ETH Zürich, Schwerzenbach, Switzerland

Abstract

To liberate fatty acids (FAs) from intracellular stores,lipolysis is regulated by the activity of the lipases adipose triglyceridelipase (ATGL), hormone-sensitive lipase and monoacylglycerol lipase. ExcessiveFA release as a result of uncontrolled lipolysis results in lipotoxicity, whichcan in turn promote the progression of metabolic disorders. However, whethercells can directly sense FAs to maintain cellular lipid homeostasis is unknown.Here we report a sensing mechanism for cellular FAs basedon peroxisomal degradation of FAs and coupled with reactive oxygen species(ROS) production, which in turn regulates FA release by modulatinglipolysis. Changes in ROS levels are sensed by PEX2, which modulates ATGLlevels through post-translational ubiquitination. We demonstrate the importanceof this pathway for non-alcoholic fatty liver disease progression using geneticand pharmacological approaches to alter ROS levels in vivo, whichcan be utilized to increase hepatic ATGL levels and ameliorate hepaticsteatosis. The discovery of this peroxisomal β-oxidation-mediated feedbackmechanism, which is conserved in multiple organs, couples the functions ofperoxisomes and lipid droplets and might serve as a new way to manipulatelipolysis to treat metabolic disorders.

Microbialmetabolite delta-valerobetaine is a diet-dependent obesogen

一作：Ken H.Liu, Joshua A. Owens, Bejan Saeedi，PI：AndrewS. Neish, Dean P. Jones

发表单位：Divisionof Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine

Abstract

Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome–host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-germ-free conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is producedby diverse bacte- rial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chainacyl-coenzyme As. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with a westerndiet but not control diet. Thus, VB provides a molecular target to understandand potentially manage microbiome–host symbiosis or dysbiosis in diet-dependent obesity.