scholarly journals Lkb1 suppresses amino acid-driven gluconeogenesis in the liver

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pierre-Alexandre Just ◽  
Sara Charawi ◽  
Raphaël G. P. Denis ◽  
Mathilde Savall ◽  
Massiré Traore ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glucose Production ◽  
Whole Body ◽  
Postprandial Period ◽  
Key Factor ◽  
Liver Kinase B1 ◽  
Whole Body Metabolism ◽  
Specific Deletion

AbstractExcessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.

scholarly journals Interactive effects of aging and aerobic capacity on energy metabolism–related metabolites of serum, skeletal muscle, and white adipose tissue

GeroScience ◽  
2021 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Timo Törmäkangas ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
White Adipose Tissue ◽  
Aerobic Capacity ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Disease Risk ◽  
Whole Body ◽  
Whole Body Metabolism

AbstractAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial β-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.

scholarly journals Role of Nutrient and Energy Sensors in the Development of Type 2 Diabetes

2021 ◽  
Author(s):  
Verónica Hurtado-Carneiro ◽  
Ana Pérez-García ◽  
Elvira Álvarez ◽  
Carmen Sanz
Keyword(s):  
Type 2 Diabetes ◽  
Nutrient Availability ◽  
Energy Demand ◽  
Metabolic Response ◽  
Whole Body ◽  
Key Factor ◽  
Control Food ◽  
Control Food Intake

Cell survival depends on the constant challenge to match energy demands with nutrient availability. This process is mediated through a highly conserved network of metabolic fuel sensors that orchestrate both a cellular and whole-body energy balance. A mismatch between cellular energy demand and nutrient availability is a key factor in the development of type 2 diabetes, obesity, metabolic syndrome, and other associated pathologies; thus, understanding the fundamental mechanisms by which cells detect nutrient availability and energy demand may lead to the development of new treatments. This chapter reviews the role of the sensor PASK (protein kinase with PAS domain), analyzing its role in the mechanisms of adaptation to nutrient availability and the metabolic response in different organs (liver, hypothalamus) actively cooperating to control food intake, maintain glycaemia homeostasis, and prevent insulin resistance and weight gain.

scholarly journals Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation

2019 ◽  
Vol 74 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Dan Yang ◽  
Yifan Yang ◽  
Yanlin Li ◽  
Rui Han
Keyword(s):  
Type 2 Diabetes ◽  
Exercise Therapy ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Mechanism Study ◽  
Physiological Mechanisms ◽  
Glycolipid Metabolism ◽  
Randomized Controlled Studies

Background: Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. Summary: Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. Key Messages: More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.

scholarly journals Genes and Diet in the Prevention of Chronic Diseases in Future Generations

2020 ◽  
Vol 21 (7) ◽  
pp. 2633 ◽  
Author(s):  
Marica Franzago ◽  
Daniele Santurbano ◽  
Ester Vitacolonna ◽  
Liborio Stuppia
Keyword(s):  
Human Health ◽  
Dietary Intervention ◽  
Nutrient Requirements ◽  
Metabolic Disturbances ◽  
Transgenerational Transmission ◽  
Key Factor ◽  
Dietary Components ◽  
Diabetes Gestational

Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.

scholarly journals Perspective: Mitochondria-ER Contacts in Metabolic Cellular Stress Assessed by Microscopy

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 5 ◽  
Author(s):  
Alessandra Stacchiotti ◽  
Gaia Favero ◽  
Antonio Lavazza ◽  
Raquel Garcia-Gomez ◽  
Maria Monsalve ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Calcium Ions ◽  
Metabolic Diseases ◽  
Cellular Stress ◽  
Pivotal Role ◽  
Whole Body ◽  
Oxygen Species ◽  
Whole Body Metabolism

The interplay of mitochondria with the endoplasmic reticulum and their connections, called mitochondria-ER contacts (MERCs) or mitochondria-associated ER membranes (MAMs), are crucial hubs in cellular stress. These sites are essential for the passage of calcium ions, reactive oxygen species delivery, the sorting of lipids in whole-body metabolism. In this perspective article, we focus on microscopic evidences of the pivotal role of MERCs/MAMs and their changes in metabolic diseases, like obesity, diabetes, and neurodegeneration.

scholarly journals A Novel Isolate with Deletion inGP3Gene of Porcine Reproductive and Respiratory Syndrome Virus from Mid-Eastern China

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Baochao Fan ◽  
Hai Wang ◽  
Juan Bai ◽  
Lili Zhang ◽  
Ping Jiang
Keyword(s):  
Amino Acid ◽  
Nucleotide Sequence ◽  
Large Scale ◽  
Eastern China ◽  
Respiratory Syndrome Virus ◽  
Pig Farm ◽  
Prrsv Strain ◽  
Full Length Genome

PRRSV strain SH1211 was isolated from the lung tissue of a piglet on a large-scale pig farm with approximately 30% morbidity and 50% mortality in mid-eastern China in 2012. The full-length genome of SH1211 was 15 313 nt in size, excluding the polyadenylated sequences, and shared 94.9% nucleotide sequence identity with the HP-PRRSV strain, JXA1. The GP2 and GP5 proteins of SH1211 shared only 91.5% and 85.1% amino acid sequence identities with those of the JXA1, respectively. A deletion at amino acid positions 68 and 69 was identified in the GP3 protein of SH1211, compared with the GP3 of Type-2 PRRSV isolates. A phylogenetic tree based on the nucleotide sequence of the complete genome showed that SH1211 is the most closely related to other HP-PRRSV strains isolated in China. However, phylogenetic analysis based on the GP2 and GP5 proteins showed that SH1211 is the most closely related to the QYYZ strain. A recombination analysis indicated that SH1211 might have been generated through recombination events between the JXA1 and QYYZ in which the GP2 and GP5 coding sequences were exchanged. Thus, SH1211 is a novel PRRSV strain with significant variation. Our analysis of SH1211 provides insight into the role of genetic variation in the antigenicity of PRRSVs in China.

scholarly journals Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324603
Author(s):  
Laura Krieg ◽  
Konrad Didt ◽  
Isabel Karkossa ◽  
Stephan H Bernhart ◽  
Stephanie Kehr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gastric Bypass Surgery ◽  
Whole Body ◽  
Expression Levels ◽  
Entire Cohort ◽  
Fat Depots ◽  
Systemic Insulin Resistance ◽  
Whole Body Metabolism

ObjectiveHuman white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism.DesignMesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR.ResultsWhile mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels.ConclusionMulti-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.

scholarly journals Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

2020 ◽  
Author(s):  
Yongtao Liu ◽  
Xuanzhen Pan ◽  
Yuanrui Hua ◽  
Yunlong Wang ◽  
Youhe Gao
Keyword(s):  
Amino Acid ◽  
Age Groups ◽  
Young Group ◽  
Whole Body ◽  
Amino Acid Substitutions ◽  
Label Free ◽  
Random Group ◽  
Age Related ◽  
Whole Body Metabolism ◽  
Aging Mechanisms

AbstractAging is an inevitable course of life. Additionally, the risk of chronic diseases or cancer increases with age. The comprehensive identification of signs related to aging can be beneficial for the prevention and early diagnosis of geriatric diseases. The comparison of global modifications in the urine proteome is a means of multidimensional information mining. This approach is based on urine, in which changes from whole-body metabolism can accumulate. This study used the urine of healthy people at different ages (22 children, 10 young people, 6 senior people) as the research object and using high-resolution tandem mass spectrometry, label-free quantitation combined with non-limiting modification identification algorithms and random group test, compared the differences in protein chemical modifications among three groups. The results show that multi-sites oxidative modifications and amino acid substitutions are noticeable features that distinguish these three age groups of people. The proportion of multi-site oxidations in urine proteins of senior (29.76%) is significantly higher than the young group (13.71% and 12.97%), which affect the biological processes of various proteins. This study could provide a reference for studies of aging mechanisms and biomarkers of age-related disease.

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