Autophagy in Myf5+ progenitors regulates energy and glucose homeostasis through control of brown fat and skeletal muscle development

Macroautophagy (MA) regulates cellular quality control and energy balance. For example, loss of MA in aP2-positive adipocytes converts white adipose tissue (WAT) into brown adipose tissue (BAT)-like, enhancing BAT function and thereby insulin sensitivity. However, whether MA regulates early BAT development is unknown. We report that deleting Atg7 in myogenic Myf5+ progenitors inhibits MA in Myf5-cell-derived BAT and muscle. Knock out (KO) mice have defective BAT differentiation and function. Surprisingly, their body temperature is higher due to WAT lipolysis-driven increases in fatty acid oxidation in 'Beige' cells in inguinal WAT, BAT and muscle. KO mice also present impaired muscle differentiation, reduced muscle mass and glucose intolerance. Our studies show that ATG7 in Myf5+ progenitors is required to maintain energy and glucose homeostasis through effects on BAT and muscle development. Decreased MA in myogenic progenitors with age and/or overnutrition might contribute to the metabolic defects and sarcopenia observed in these conditions

Epidemiological characteristics analysis of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020

ObjectiveTo analyze the epidemiological characteristics of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020， and put forward relevant regulatory suggestions.MethodsThrough the National Foodborne Disease Outbreak Monitoring System， the data of foodborne disease outbreaks caused by takeaway in China’s Mainland from 2010 to 2020 were collected and analyzed， and descriptive epidemiological characteristics were performed.ResultsA total of 549 foodborne disease outbreaks caused by takeaway were reported in China’s Mainland （except Tibet Autonomous Region） from 2010 to 2020， resulting in 9 285 illnesses and 2 deaths. The largest number of outbreaks and illnesses was in the third quarter， accounting for 41.53% and 44.58% of the total respectively. Except the unknown pathogenic factors， the number of outbreaks and illnesses caused by microbial pathogenic factors were the highest， accounting for 39.16% and 60.26% of the total respectively. Except the unknown suspected food， the number of outbreaks and illnesses caused by mixed food and multiple food were higher， accounting for 21.86% and 15.12% of the outbreaks respectively， and accounting for 20.58% and 13.10% of the number of illnesses respectively. Except the unknown food source， the top 3 food source were school canteens， collective dining delivery units/central kitchens and fast food restaurants， the number of outbreaks accounted for 20.04%， 15.66% and 15.48% respectively， and the number of illnesses accounted for 35.30%， 17.52% and 10.57% respectively. Except the multiple factors and unknown factors， the number of outbreaks caused by improper storage were the highest accounting for 8.74%， and the number of illnesses caused by improper processing accounted for 7.74%.ConclusionMicrobial growth and reproduction due to improper storage and processing is the major cause of foodborne disease outbreaks caused by takeaway. It is suggested that the food safety supervision and administration departments should strengthen the whole process supervision and management of takeaway， establish and ensure catering services strictly abide by the good hygiene operations according to food raw in materials， production， transportation， distribution and other aspects， so as to effectively prevent and control the occurrence foodborne diseases

Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure.

Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc–modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease

Transcription Factor EB Controls Metabolic Flexibility during Exercise

The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism

Adipocyte-Specific IKKβ Signaling Suppresses Adipose Tissue Inflammation through an IL-13-Dependent Paracrine Feedback Pathway

Summary: Adipose tissue inflammation is one pathway shown to mediate insulin resistance in obese humans and rodents. Obesity induces dynamic cellular changes in adipose tissue to increase proinflammatory cytokines and diminish anti-inflammatory cytokines. However, we have found that anti-inflammatory interleukin-13 (IL-13) is unexpectedly induced in adipose tissue of obese humans and high-fat diet (HFD)-fed mice, and the source of IL-13 is primarily the adipocyte. Moreover, HFD-induced proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and IL-1β mediate IL-13 production in adipocytes in an IKKβ-dependent manner. In contrast, adipocyte-specific IKKβ-deficient mice show diminished IL-13 expression and enhanced inflammation after HFD feeding, resulting in a worsening of the insulin-resistant state. Together these data demonstrate that although IKKβ activates the expression of proinflammatory mediators, in adipocytes, IKKβ signaling also induces the expression of the anti-inflammatory cytokine IL-13, which plays a unique protective role by limiting adipose tissue inflammation and insulin resistance. : IKKβ is known to be a proinflammatory mediator. However, IKKβ in adipocytes also mediates IL-13 expression to suppress high-fat-diet-induced inflammation in adipose tissue. This feedback mechanism may be the molecular basis of diet-induced chronic low-grade inflammation, resulting in systemic insulin resistance

Magma Recharge and Reactive Bulk Assimilation in Enclave-Bearing Granitoids, Tonglu, South China

Magmatic processes leading to granitoid formation are of relevance to the evolution of continental crust and its mineralization. A comprehensive study of field observations with whole-rock and in situ mineral chemical and isotopic compositions was carried out on granitoids, mafic microgranular enclaves (MME) and country-rock xenoliths (CRX) from Tonglu, South China to constrain the magmatic processes operating. Zircon U-Pb geochronology indicates that the MME and granitoids formed coevally at similar to 130 Ma. Petrographic observations suggest that the MME are quenched mafic clots formed during incomplete magma mixing. The different zircon Hf isotopic compositions of the MME (eHf(t) 1/4 -4.0 to -0.7) and the host granitoids (epsilon(Hf)(t) = -8.1 to -1.7) indicate mingling between mafic and felsic magmas from different sources. The CRX are composed of fresh cores and dark rims. The pyroxene-rich fresh cores are depleted in Rb, Ba and K while the biotite-rich dark rims show obvious enrichments in Rb, Ba and K, indicating modification by hydrous K-rich felsic melts or fluids from the host magma. In contrast, some large CRX have embayed structures and are surrounded by several small, biotite-rich CRX, suggesting disaggregation and modification of large CRX into the host magma. The occurrence of abundant felsic magmatic veinlets in the CRX implies that they could have experienced brittle deformation in the cold shallow crust, which agrees with an emplacement depth of about 5 km estimated using Al-in hornblende geobarometry. The high Sr-87/(86)Sri (0.7129) and low eNd(t) (-10.2) values imply that these CRX were derived from the upper continental crust. All these features suggest a typical reactive bulk assimilation process. Microanalysis of Sr-87/Sr-86 ratios in plagioclase from the Tonglu granitoids vary over a large range (0.7073-0.7137) with complex rim-core-rim variations, which resulted from open-system processes. Given the variation in Sr isotopes, four types of plagioclase were identified. Type I plagioclase are homogeneous in terms of Sr-87/Sr-86, suggesting normal crystal fractionation. Recharge of mafic magma injecting into felsic magma resulted in the core-mantle variations of type II plagioclases. Albitic cores with high Sr-87/Sr-86 (up to 0.7092) indicate felsic magma with highly radiogenic Sr (Sr-87/Sr-86> 0.7092). Influx of mafic magma with less radiogenic Sr (Sr-87/Sr-86<0.7080) resulted in a decrease in Sr-87/Sr-86 and an abrupt increase of An contents (similar to An(30) to similar to An(60)) from core to mantle. Type III plagioclase are distinguished by lower Sr-87/Sr-86 ratios in the core (0.7084-0.7086) and significantly more radiogenic Sr at the rim (0.7097-0.7112), which is attributed to the assimilation of the country rocks. Core-mantle-rim variations in type IV plagioclase not only record magma recharge events, but also crustal assimilation. Increasing An values and decreasing Sr-87/Sr-86 ratios (down to 0.7075) from core to mantle and significantly more radiogenic Sr (up to 0.7117) in the outer rim suggest that the recharge event took place prior to the assimilation of ancient crustalNational Nature Science Foundation of China [41530211]; MLR special funds for public welfare projects [201211013-2]; State Administration of Foreign Expert Affairs of China [B07039]; MOST special funds of the State Key Laboratory of Geological Processes and Mineral Resources [MSFGPMR01]12 month embargo; published online: 08 May 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

First direct evidence of sedimentary carbonate recycling in subduction-related xenoliths

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Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn

Mice null for Fyn (a member of the Src family of nonreceptor tyrosine kinases) display a reduced percentage of adipose mass associated with decreased adipocyte cell size. In parallel, there is a substantial reduction in fasting plasma glucose, insulin, triglycerides, and free fatty acids concomitant with decreased intrahepatocellular and intramyocellular lipid accumulation. Importantly, the Fyn null mice exhibit improved glucose tolerance resulting from increased peripheral tissue (adipose and skeletal muscle) insulin sensitivity with a very small effect in the liver. Moreover, whole-body, adipose, and skeletal muscle fatty acid uptake and oxidation are increased along with AMP kinase activation and acetyl-CoA carboxylase inhibition. Together, these data demonstrate crosstalk between Src-family kinase activity and fatty acid oxidation and show that the loss of Fyn markedly improves peripheral tissue insulin sensitivity by relieving a selective negative modulation of AMP kinase activity in adipose tissue and skeletal muscle