Abstract:
BACKGROUND:Modern lifestyles, especially high-caloric intake and physical inactivity, contribute to the increased prevalence of non-alcoholic fatty liver disease (NAFLD), which becomes a significant health problem worldwide. Lifestyle changes, however, affect not only parental generation, but also their offspring, reinforcing the need for efficient preventive approaches to deal with this disease. This transgenerational influence of phenotypes dependent on parents (particularly maternal) behaviours may open additional research avenues. Despite persistent attempts to design an effective pharmacological therapy against NAFLD, physical activity, as a non-pharmacological approach, emerges as an exciting strategy. SCOPE OF REVIEW:Here we briefly review the effect of physical exercise on liver mitochondria adaptations in NAFLD, highlighting the importance of mitochondrial metabolism and transgenerational and epigenetic mechanisms in liver diseases. MAJOR CONCLUSIONS:A deeper look into cellular mechanisms sheds a light on possible effects of physical activity in the prevention and treatment of NAFLD through modulation of function and structure of particular organelles, namely mitochondria. Additionally, despite of increasing evidence regarding the contribution of epigenetic mechanisms in the pathogenesis of different diseases, the role of microRNAs, DNA methylation, and histone modification in NAFLD pathogenesis still needs to be elucidated.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Stevanović J,Beleza J,Coxito P,Ascensão A,Magalhães Jdoi
10.1016/j.molmet.2019.11.015subject
Has Abstractpub_date
2020-02-01 00:00:00pages
1-14issn
2212-8778pii
S2212-8778(19)30947-0journal_volume
32pub_type
杂志文章,评审abstract:OBJECTIVE:Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context,...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.08.007
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Functional investigation of novel gene/protein targets associated with adipocyte differentiation or function heavily relies on efficient and accessible tools to manipulate gene expression in adipocytes in vitro. Recent advances in gene-editing technologies such as CRISPR-Cas9 have not only eased gene editing ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.07.001
更新日期:2017-10-01 00:00:00
abstract:OBJECTIVE:A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work su...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.012
更新日期:2017-04-26 00:00:00
abstract:OBJECTIVE:Mutations to the BSCL2 gene disrupt the protein seipin and cause the most severe form of congenital generalised lipodystrophy (CGL). Affected individuals exhibit a near complete loss of white adipose tissue (WAT) and suffer from metabolic disease. Seipin is critical for adipocyte development in culture and mi...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.01.019
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistanc...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.101153
更新日期:2020-12-23 00:00:00
abstract:OBJECTIVE:Increasing adaptive thermogenesis by stimulating browning in white adipose tissue is a promising method of improving metabolic health. However, the molecular mechanisms underlying this transition remain elusive. Our study examined the molecular determinants driving the differentiation of precursor cells into ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101137
更新日期:2020-12-05 00:00:00
abstract:OBJECTIVE:Pancreatic β cell failure plays a central role in the development of type 2 diabetes (T2D). While the transcription factors shaping the β cell gene expression program have received much attention, the post-transcriptional controls that are activated in β cells during stress are largely unknown. We recently id...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.05.009
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular t...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2018.05.009
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE/METHODS:DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.11.003
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechan...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.01.001
更新日期:2020-05-01 00:00:00
abstract::Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of central metabolic signaling, and mice with whole brain-, leptin receptor (LepRb) expressing cell-, or proopiomelanocortin neuron-specific PTP1B-deficiency are lean, leptin hypersensitive, and display improved glucose homeostasis. However, whether the meta...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.01.008
更新日期:2014-01-19 00:00:00
abstract:BACKGROUND:Pancreatic β-cells adapt to high metabolic demand by expanding their β-cell mass and/or enhancing insulin secretion to maintain glucose homeostasis. Type 2 diabetes (T2D) is typically characterized by β-cell decompensation. SCOPE OF THE REVIEW:The current review focuses on summarizing the "omics" and "epi-o...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2019.06.003
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.03.014
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVE:Glucose-stimulated insulin secretion in pancreatic beta cells requires metabolic signals including the generation of glucose-derived short chain acyl-CoAs in the cytosol from mitochondrially-derived metabolites. One concept of insulin secretion is that ATP citrate lyase generates short chain acyl-CoAs in the ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.07.011
更新日期:2016-08-08 00:00:00
abstract:OBJECTIVE:A major challenge for obesity treatment is the maintenance of reduced body weight. Diet-induced obese mice are resistant to achieving normoweight once the obesogenic conditions are reversed, in part because lowered circulating leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that def...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.07.012
更新日期:2016-08-05 00:00:00
abstract:OBJECTIVE:Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) an...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.12.005
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.010
更新日期:2015-07-06 00:00:00
abstract::SIRT1 has attracted a lot of interest since it was discovered as a mammalian homolog of Sir2, a protein that influences longevity in yeast. Intensive early research suggested a key role of SIRT1 in mammalian development, metabolic flexibility and oxidative metabolism. However, it is the growing body of transgenic mode...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2013.10.006
更新日期:2013-10-23 00:00:00
abstract:OBJECTIVE:The enteroendocrine hormone glucagon-like peptide 1 (GLP-1) is an attractive anti-diabetic therapy. Here, we generated a recombinant Lactococcus lactis strain genetically modified to produce GLP-1 and investigated its ability to improve glucose tolerance in mice on chow or high-fat diet (HFD). METHODS:We tra...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.06.006
更新日期:2016-06-22 00:00:00
abstract:OBJECTIVE:Pharmacological activation of adenosine signaling has been shown to increase β-cell proliferation and thereby β-cell regeneration in zebrafish and rodent models of diabetes. However, whether adenosine has an endogenous role in regulating β-cell proliferation is unknown. The objective of this study was to dete...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.09.006
更新日期:2016-09-20 00:00:00
abstract::The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghreli...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.07.009
更新日期:2014-08-01 00:00:00
abstract::The lipin protein family of phosphatidate phosphatases has an established role in triacylglycerol synthesis and storage. Physiological roles for lipin-1 and lipin-2 have been identified, but the role of lipin-3 has remained mysterious. Using lipin single- and double-knockout models we identified a cooperative relation...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2013.11.008
更新日期:2013-11-28 00:00:00
abstract::Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2012.08.006
更新日期:2012-08-17 00:00:00
abstract:OBJECTIVE:Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS:Here we first determined that the cis conformation of the succinate backbone is preferred and ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.09.005
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:Adaptive thermogenesis, which is partly mediated by sympathetic input on brown adipose tissue (BAT), is a mechanism of heat production that confers protection against prolonged cold exposure. Various endogenous stimuli, for example, norepinephrine and FGF-21, can also promote the conversion of inguinal white ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101052
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.05.006
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the meta...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101145
更新日期:2020-12-19 00:00:00
abstract:OBJECTIVES:Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid species transported into the brain, their effects on energy balance, and the mechanisms by which they regulate activity of hypothalamic neurons...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.01.002
更新日期:2020-04-01 00:00:00
abstract:OBJECTIVE:Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.06.013
更新日期:2016-06-30 00:00:00
abstract:OBJECTIVE:In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycoly...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.08.003
更新日期:2017-11-01 00:00:00