Featured
-
-
Article
| Open AccessIron mobilization during lactation reduces oxygen stores in a diving mammal
Here, the authors show that Weddell seal mothers mobilize endogenous iron stores during lactation to provide to pups, resulting in iron concentrations in milk 100x higher than terrestrial mammals. This was associated with reduced dive durations in the mother, a cost of reproduction.
- Michelle R. Shero
- , Amy L. Kirkham
- & Jennifer M. Burns
-
Article
| Open AccessPhenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ
Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset.
- Qian Zhou
- , Wan-Wan Sun
- & Shi-Min Zhao
-
Article
| Open AccessA temperature-regulated circuit for feeding behavior
Feeding behavior is modulated by ambient temperature, as lower temperatures increase the necessity for energy intake and vice versa. Here the authors identify neuronal pathways that control feeding in a temperature-dependent manner.
- Shaowen Qian
- , Sumei Yan
- & Yi Zhou
-
Article
| Open AccessLoss of immunity-related GTPase GM4951 leads to nonalcoholic fatty liver disease without obesity
Obesity is a major risk factor for fatty liver disease. Here, using a forward genetic screen, the authors identify the gene GM4951 as a GTPase involved in lipid oxidation and development of NAFLD in mice.
- Zhao Zhang
- , Yu Xun
- & Bruce Beutler
-
Article
| Open AccessHepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis
Excess ketogenesis can lead to ketoacidosis, a serious complication in patients with diabetes. Here the authors report an insulin independent pathway, the hepatic nonparenchymal S100A9-TLR4-mTORC1 axis, that is able to normalize diabetic ketogenesis and pre-clinical data to suggest potential for development of S100A9 based adjunctive therapy to insulin.
- Gloria Ursino
- , Giorgio Ramadori
- & Roberto Coppari
-
Article
| Open AccessAdipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism
Dysregulation of plasmalogen metabolism in adipose tissue is associated with metabolic diseases. Here the authors characterize the role of adipocyte TMEM86A as a lysoplasmalogenase and show its deletion is protective against high fat diet induced metabolic disease, an effect that can be recapitulated by plasmenyl lysophosphatidylethanolamine 18:0 supplementation.
- Yoon Keun Cho
- , Young Cheol Yoon
- & Yun-Hee Lee
-
Article
| Open AccessTranslational fidelity and growth of Arabidopsis require stress-sensitive diphthamide biosynthesis
Diphthamide is a post-translationally modified histidine residue present in animal and yeast TRANSLATION ELONGATION FACTOR2. Here the authors show that diphthamide modification of eEF2 is conserved in Arabidopsis thaliana and contributes to translational fidelity and growth via cell proliferation.
- Hongliang Zhang
- , Julia Quintana
- & Ute Krämer
-
Article
| Open AccessTRIM24 is an insulin-responsive regulator of P-bodies
Insulin promotes hepatic lipogenesis, though underlying regulation remains unclear. Here the authors show that insulin translocates TRIM24 from the nucleus into cytosolic P-bodies to stabilise hepatic Pparγ mRNA, and that inactivation of TRIM24 promotes Pparγ degradation and alleviates hepatosteatosis.
- Wen Wei
- , Qiaoli Chen
- & Shuai Chen
-
Article
| Open AccessCardiac disruption of SDHAF4-mediated mitochondrial complex II assembly promotes dilated cardiomyopathy
Functional succinate dehydrogenase (SDH) complex is vital to mitochondrial homeostasis. Here the authors show that disruption of SDH assembly in the heart causes dilated cardiomyopathy via impairing the mitochondrial integrity and metabolism and that mitochondrial interventions can be an effective approach to ameliorate the disease progression.
- Xueqiang Wang
- , Xing Zhang
- & Zhihui Feng
-
Article
| Open AccessSex differences in heart mitochondria regulate diastolic dysfunction
In this paper, the authors show that sex differences in mitochondrial DNA levels and function in the heart contribute to sex biases in functions relevant to heart failure, identifying Acsl6 as a mitochondrial sex-biased regulator of diastolic function.
- Yang Cao
- , Laurent Vergnes
- & Aldons J. Lusis
-
Article
| Open AccessTight junction channel regulation by interclaudin interference
Tight junctions are formed by claudin proteins that can be classified as pore- or barrier-forming. Here, Shashikanth et al. report a third function, termed interclaudin interference, in which one claudin inhibits pore function of another claudin by disrupting its polymeric complexes.
- Nitesh Shashikanth
- , Marion M. France
- & Jerrold R. Turner
-
Article
| Open AccessPancreatic α and β cells are globally phase-locked
The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells are critical in glucose homeostasis. Here the authors show that the Ca2+ oscillations of α and β cells are phase-locked, and that the oscillation pattern is tuned by paracrine interactions between α and β cells.
- Huixia Ren
- , Yanjun Li
- & Chao Tang
-
Article
| Open AccessMicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake
The microRNA miR-21 is induced in the islets of patients with glucose intolerance and diabetic mice. Here the authors report that deletion of miR-21 in pancreatic β-cells impairs glucose-stimulated insulin secretion via reduced glucose uptake, while a miR-21 agomir reduces blood glucose leves in diabetic male mice.
- Ruiling Liu
- , Cuilian Liu
- & Qingguo Ruan
-
Article
| Open AccessA randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes
Evidence from preclinical models suggest that lowering levels of branched chain amino acids (BCAA) improves glucose metabolism. Here the authors report that NaPB, an accelerator of BCAA catabolism, improves peripheral insulin sensitivity in patients with type 2 diabetes in a randomized placebo-controlled crossover clinical trial.
- Froukje Vanweert
- , Michael Neinast
- & Esther Phielix
-
Article
| Open AccessAdipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling
Kynurenine, a tryptophan metabolite, is increased in the circulating plasma of obese individuals, but the source has been unclear. Here, the authors show in mice that mature adipocytes produce kynurenine, with vitamin B6 administration preventing accumulation and protecting against high-fat diet.
- Teng Huang
- , Jia Song
- & Cong-Yi Wang
-
Article
| Open AccessA hexa-species transcriptome atlas of mammalian embryogenesis delineates metabolic regulation across three different implantation modes
Mammalian embryogenesis relies on glycolysis and oxidative phosphorylation, but understanding of the dynamics of metabolic regulation in the postimplantation embryo in vivo remains elusive. Here the authors compile single-cell embryo profiling data in six mammalian species and reveal a conserved metabolic programme despite different implantation modes.
- Anna Malkowska
- , Christopher Penfold
- & Thorsten E. Boroviak
-
Article
| Open AccessTriiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation
Thyroid hormone (TH) action regulates brown adipose tissue thermogenic capacity through incompletely understood mechanisms. Here the authors report that T3, the active form of TH, increases thermogenic capacity via thyroid hormone receptor α-mediated hyperplasia of brown adipose tissue adipocyte progenitor cells.
- Shengnan Liu
- , Siyi Shen
- & Hao Ying
-
Article
| Open AccessAdipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
Thermogenic adipocytes maintain body temperature in response to cold, but how this is tuned during cold and re-warming is unclear. Here, the authors show HIF2α inhibits beige adipocyte retention, regulating PKA catalysis to control dynamic adipocyte remodelling.
- Ji Seul Han
- , Yong Geun Jeon
- & Jae Bum Kim
-
Article
| Open AccessThe long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase
Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.
- Alastair G. Kerr
- , Zuoneng Wang
- & Hui Gao
-
Article
| Open AccessO-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine
Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation.
- Kibum Kim
- , Hee Chan Yoo
- & Jung Min Han
-
Article
| Open AccessInfluence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration
Impaired mitochondrial function in liver tissue may contribute to the pathogenesis and disease progression of nonalcoholic fatty liver disease (NAFLD). Here the authors report that patients with obesity have lower mitochondrial capacity in adipose tissues but higher capacity in the liver, without overall associations to NAFLD severity, and that bariatric surgery increases hepatic mitochondrial respiration and mitochondrial biogenesis.
- Julie S. Pedersen
- , Marte O. Rygg
- & Flemming Dela
-
Comment
| Open AccessMetabolic regulation by the intestinal metformin-AMPK axis
AMP-activated protein kinase (AMPK) mediates the glucose-lowering effect of the antidiabetic agent metformin, but the sites of action remain unclear. In the March issue of Nature Communications, Zhang and colleagues reported that intestinal epithelium-specific AMPKα1 knockout mice fail to respond to metformin and exhibit disruption in metabolic homeostasis secondary to changes in the gut microbiome. This highlights a therapeutic potential of targeting intestinal AMPK for diabetes.
- Song-Yang Zhang
- & Tony K. T. Lam
-
Article
| Open AccessProteome allocations change linearly with the specific growth rate of Saccharomyces cerevisiae under glucose limitation
Understanding how yeast organizes its functional proteome is a fundamental task in systems biology. Here, the authors conduct a multiomics analysis on yeast cells cultured with different growth rates, identifying a linear dependence of the functional proteome on the growth rate.
- Jianye Xia
- , Benjamin J. Sánchez
- & Jens Nielsen
-
Article
| Open AccessStatin therapy inhibits fatty acid synthase via dynamic protein modifications
Statin therapy is associated with numerous cellular effects. Here, the authors show that statin treatment increases post-translational modifications on fatty acid synthase in the active site, revealing communication between the cholesterol and lipid biosynthetic pathways.
- Alec G. Trub
- , Gregory R. Wagner
- & Matthew D. Hirschey
-
Article
| Open AccessA reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans
Mitochondria regulate diverse cellular signalling processes in addition to producing energy. Here, the authors show a mitochondrial redox switch that, when activated, helps nematode worms sense conditions of low environmental oxygen.
- John O. Onukwufor
- , M. Arsalan Farooqi
- & Andrew P. Wojtovich
-
Article
| Open AccessMitofusin 1 and 2 regulation of mitochondrial DNA content is a critical determinant of glucose homeostasis
Sidarala et al. examine the importance of the mitochondrial structural proteins, Mitofusins 1 and 2 (Mfn1/2), in diabetes. They find that Mfn1/2 control blood glucose by preserving mitochondrial DNA content, rather than mitochondrial structure.
- Vaibhav Sidarala
- , Jie Zhu
- & Scott A. Soleimanpour
-
Article
| Open AccessEnhancement of anaerobic glycolysis – a role of PGC-1α4 in resistance exercise
Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, the authors show that an RET-induced increase in PGC-1α4 expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions.
- Jin-Ho Koh
- , Mark W. Pataky
- & K. Sreekumaran Nair
-
Article
| Open AccessDistinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle
The anti-aging intervention calorie restriction (CR) is thought to act via the nutrient-sensing multiprotein complex mTORC1. Here the authors show that the mTORC1-inhibitor rapamycin and CR use largely distinct mechanisms to slow mouse muscle aging.
- Daniel J. Ham
- , Anastasiya Börsch
- & Markus A. Rüegg
-
Article
| Open AccessInsulin action and resistance are dependent on a GSK3β-FBXW7-ERRα transcriptional axis
The downstream mechanisms involved in insulin signaling and resistance remain incompletely understood. Here the authors report that insulin-dependent dephosphorylation stabilizes ERRα via the GSK3β/FBXW7 axis, and disruption of this post-translational mechanism results in insulin resistance in mice.
- Hui Xia
- , Charlotte Scholtes
- & Vincent Giguère
-
Article
| Open AccessFGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice
The restriction of dietary protein or amino acid intake is well established to extend lifespan in multiple species. Here, the authors show that the endocrine hormone FGF21 is necessary for dietary protein restriction to extend lifespan and improve metabolic health in aged, male mice.
- Cristal M. Hill
- , Diana C. Albarado
- & Christopher D. Morrison
-
Article
| Open AccessMitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice
Senescent cells play a role in pathogenesis of diabetes, and senolytic agents can improve obesity- and diabetes-related pathologies. Here the authors report that mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, alleviates symptoms of obesity and prediabetes in mice, potentially via reduction of food intake and elimination of senescent cells.
- Eliska Vacurova
- , Jaroslava Trnovska
- & Jiri Neuzil
-
Article
| Open AccessLong-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle
Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.
- Ben D. McNally
- , Dean F. Ashley
- & Lee D. Roberts
-
Article
| Open AccessAdipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice
Obesity impairs regulation of adipocyte lipolysis, which contributes towards development of insulin resistance. Here the authors report that adipocyte Gq signaling functions as a regulator of lipolysis and systemic glucose and lipid homeostasis in mice, suggesting that agents able to stimulate this pathway may prove useful as antidiabetic drugs.
- Takefumi Kimura
- , Sai P. Pydi
- & Jürgen Wess
-
Article
| Open AccessGenetic variation of macronutrient tolerance in Drosophila melanogaster
Responses to diet composition may be linked to susceptibility to metabolic diseases such as type 2 diabetes. Here the authors report that Drosophila melanogaster displays genetic variation in survival on different diets and describe the importance for JNK-pathway and a conserved orphan nuclear hormone receptor tailless in regulating sugar tolerance.
- E. Havula
- , S. Ghazanfar
- & A. M. Senior
-
Article
| Open AccessLysosomal Ca2+-mediated TFEB activation modulates mitophagy and functional adaptation of pancreatic β-cells to metabolic stress
Autophagy is important for pancreatic β-cell function, however, the role of mitophagy and mechanism for mitophagy in β-cells are unclear. Here the authors report that in stressed β-cells, lysosomal Ca2+ release promotes mitophagy via activation of the transcription factor EB (TFEB) and loss of β-cell TFEB aggravates glucose intolerance during high-fat diet.
- Kihyoun Park
- , Hyejin Lim
- & Myung-Shik Lee
-
Article
| Open AccessDeep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control
Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, but the connecting pathophysiological mechanisms are incompletely understood. Here the authors identify arylsulfatase A as a NASH-induced hepatokine that inhibits hepatic lysophosphatidylcholine and lysophosphatidic acid secretion, and improves muscle insulin action and systemic glucose homeostasis.
- Magdalene K. Montgomery
- , Jacqueline Bayliss
- & Matthew J. Watt
-
Article
| Open AccessIntestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis
Mammalian 5′-AMP-activated protein kinase (AMPK) is a nutrient sensor and a therapeutic target for Type 2 Diabetes. Here the authors report that intestinal AMPK modulates brown adipose tissue thermogenesis through anti-microbial peptide controlled gut microbiota and may partially underlie the anti-diabetic effects of metformin.
- Eryun Zhang
- , Lihua Jin
- & Wendong Huang
-
Article
| Open AccessExploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes
Oral verapamil lowers inflammatory markers and daily insulin needs in subjects with type 1 diabetes and helps preserve pancreatic beta cell function for at least two years. In this context, serum chromogranin A provides a promising therapy marker.
- Guanlan Xu
- , Tiffany D. Grimes
- & Anath Shalev
-
Article
| Open AccessKindlin-2 haploinsufficiency protects against fatty liver by targeting Foxo1 in mice
Here, the authors show that expression of kindlin-2 is increased in patients with nonalcoholic fatty liver disease (NAFLD). In mouse models, specific deletion of kindlin-2 in liver ameliorates, while its overexpression exacerbates, NAFLD by modulating Foxo1 in hepatocytes.
- Huanqing Gao
- , Liang Zhou
- & Guozhi Xiao
-
Article
| Open AccessRandomized controlled trial for time-restricted eating in healthy volunteers without obesity
Time-restricted eating, both early (eTRF) and mid-day (mTRF), have been shown to have metabolic benefits. Here the authors report a randomized controlled trial to compare the effects of eTRF and mTRF in healthy volunteers without obesity, and find that eTRF is more effective in improving the primary outcome insulin sensitivity.
- Zhibo Xie
- , Yuning Sun
- & Yilei Mao
-
Article
| Open AccessDisuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength
Mitochondrial function is important for muscle maintenance and function, and mitochondrial proteolysis maintains mitochondrial integrity and function. Here the authors report that that loss of LONP1-dependent mitochondrial proteolysis in muscle causes reduced muscle mass and strength via activation of autophagy.
- Zhisheng Xu
- , Tingting Fu
- & Zhenji Gan
-
Article
| Open AccessComparative metabolomics with Metaboseek reveals functions of a conserved fat metabolism pathway in C. elegans
Untargeted mass spectrometry-based metabolomics can reveal new biochemistry, but data analysis is challenging. Here, the authors develop Metaboseek, an open-source software that facilitates metabolite discovery, and apply it to characterize fatty acid alpha-oxidation in C. elegans.
- Maximilian J. Helf
- , Bennett W. Fox
- & Frank C. Schroeder
-
Article
| Open AccessSmall molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes
Type 2 diabetes is associated with insulin resistance, impaired insulin secretion and liver steatosis. Here the authors report a proof-of-concept study for small molecule SWELL1 modulators as a therapeutic approach to treat diabetes and associated liver steatosis by enhancing systemic insulin-sensitivity and insulin secretion in mice.
- Susheel K. Gunasekar
- , Litao Xie
- & Rajan Sah
-
Article
| Open AccessCaffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance
Caffeine may reduce cardiovascular disease risk, but the underlying mechanisms for these effects are incompletely understood. Here the authors report that caffeine inhibits the activation of the transcription factor SREBP2 to promote LDLc clearance through the PCSK9-LDLR axis.
- Paul F. Lebeau
- , Jae Hyun Byun
- & Richard C. Austin
-
Article
| Open AccessBeta-cell specific Insr deletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance
Insulin receptor protein is present in pancreatic β-cells, but the consequences of β-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.
- Søs Skovsø
- , Evgeniy Panzhinskiy
- & James D. Johnson
-
Article
| Open AccessThe gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress
Intestinal nutrient-sensing is important in metabolic control. Here the authors show that the gut-derived hormone Allatostatin C, a somatostatin homolog in fruit flies, links enteric nutrient sensing to behavioral and metabolic adaptations that maintain energetic homeostasis in Drosophila melanogaster.
- Olga Kubrak
- , Takashi Koyama
- & Kim Rewitz
-
Article
| Open AccessMitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis
Mitochondrial function is linked to lifespan. Here the authors show that inhibition of mitochondrial protein import leads to a reduction in mitochondrial abundance and extends lifespan in Caenorhabditis elegans via activation of glycolysis and de novo serine biosynthesis.
- Eirini Lionaki
- , Ilias Gkikas
- & Nektarios Tavernarakis
-
Article
| Open AccessAccumulation of microbial DNAs promotes to islet inflammation and β cell abnormalities in obesity in mice
Obesity is associated with increased gut permeability, and microbial products that are leaked from the gut may contribute towards obesity-associated inflammation. Here the authors show that the leakage of gut extracellular vesicles containing microbial DNA leads to bacterial DNA accumulation in pancreatic β-cells, promoting obesity-associated islet inflammation.
- Hong Gao
- , Zhenlong Luo
- & Wei Ying
-
Article
| Open AccessMacrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Bingyang Dai
- , Jiankun Xu
- & Ling Qin