Dendrobium species regulate energy homeostasis in neurodegenerative diseases: a review

Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabolic disorders and related neurodegenerative diseases.Dendrobium species(‘Shihu’in Chinese)such as D.officinale,D.huoshanense,D.nobile,D.chrysanthum,D.loddigesii,D.moniliforme,D.gratiosissimum,D.candidum and D.caulis are widely used as traditional Chinese medicines/nutraceuticals to control and treat neurodegenerative disorders.These dietary herbs and their derived compounds possess a variety of biological properties,such as suppression of oxidative stress and neuroinflammation,regulation of energy homeostasis mainly through improving brain mitochondria function,insulin signaling and lipid metabolism.Furthermore,they reduce neurotoxicity,alleviate brain injury and neuropathy,and prevent neurodegenerative conditions including stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease in humans and/or rodents.Moreover,the nutraceuticals from Dendrobium species promote gut health and aid digestion,which appear to be associated with beneficial effects on brain energy homeostasis.Based on the above-mentioned health benefits associated with Dendrobium species,this work reviews their nutraceutical role in neurodegenerative disorders and further suggests the need to elucidate mechanisms of the underlying molecular actions.

The interplay between hepatocyte nuclear factor 4α(HNF4α)and cholesterol sulfotransferase(SULT2B1b)in hepatic energy homeostasis

The nuclear receptor hepatocyte nuclear factor 4alpha(HNF4α)plays a critical role in the regulation of metabolic homeostasis,including glucose homeostasis.Sulfotransferases(SULTs)catalyze the transfer of a sulfate group from 3-phosphoadenosine 5-phosphosulfate(PAPS)to an acceptor molecule.Sulfonation plays an essential role in regulating the chemical and functional homeostasis of endogenous and exogenous molecules.Among SULTs,the cholesterol sulfotransferase 2B1b(SULT2B1b)preferentially catalyzes the sulfoconjugation of cholesterol and oxysterols to form cholesterol sulfate and oxysterol sulfates.Hepatic gluconeogenesis represents a critical component of energy metabolism.Although there have been reviews on the regulation of glucose homeostasis by HNF4a,the interplay between HNF4a and SULT2B1b in hepatic glucose homeostasis remains scattered.In this review,we intend to provide an overview on how HNF4a functionally cross-talks with SULT2B1b to regulate hepatic glucose homeostasis and whether the HNF4a-SULT2B1b axis represents a novel therapeutic target for the management of metabolic liver disease and metabolic syndrome.

Neuropeptide Y and melanocortin receptors in fish:regulators of energy homeostasis

Energy homeostasis,which refers to the physiological processes that the energy intake is exquisitely coordinated with energy expenditure,is critical for survival.Therefore,multiple and complex mechanisms have been involved in the regulation of energy homeostasis.The central melanocortin system plays an important role in modulating energy homeostasis.This system includes the orexigenic neurons,expressing neuropeptide Y/Agouti-related protein(NPY/AgRP),and the anorexigenic neurons expressing proopiomelanocortin(POMC).The downstream receptors of NPY,AgRP and post-translational products of POMC are G protein-coupled receptors(GPCRs).This review summarizes the compelling evidence demonstrating that NPY and melanocortin receptors are involved in energy homeostasis.Subsequently,the comparative studies on physiology and pharmacology of NPY and melanocortin receptors in humans,rodents and teleosts are summarized.Also,we provide a strategy demonstrating the potential application of the new ligands and/or specific variants of melanocortin system in aquaculture.

Hypothalamic GABAergic neurocircuitry in the regulation of energy homeostasis and sleep/wake control

Gamma-aminobutyric acid(GABAergic)neuron,as one of important cell types in synaptic transmission,has been widely involved in central nervous system(CNS)regulation of organismal physiologies including cognition,emotion,arousal and reward.However,upon their distribution in various brain regions,effects of GABAergic neurons in the brain are very diverse.In current report,we will present an overview of the role of GABAergic mediated inhibitory neurocircuitry in the hypothalamus,underlying mechanism of feeding and sleep homeostasis as well as the characteristics of latest transcriptome profile in order to call attention to the GABAergic system as potentially a promising pharmaceutical intervention or a deep brain stimulation target in eating and sleep disorders.

Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration

In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors(such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer’s disease and Parkinson’s disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.

Peripheral actions and direct central-local communications of melanocortin 4 receptor signaling

Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.

Neural plasticity and adult neurogenesis: the deep biology perspective

The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology.

Circulating leptin and its muscle gene expression in Nellore cattle with divergent feed efficiency

Background: Leptin has a strong relation to important traits in animal production, such as carcass composition,feed intake, and reproduction. It is mainly produced by adipose cells and acts predominantly in the hypothalamus.In this study, circulating leptin and its gene expression in muscle were evaluated in two groups of young Nellore bulls with divergent feed efficiency. Individual dry matter intake(DMI) and average daily gain(ADG) of 98 Nellore bulls were evaluated in feedlot for 70 d to determinate the residual feed intake(RFI) and select 20 animals for the high feed efficient(LRFI) and 20 for the low feed efficient(HRFI) groups. Blood samples were collected on d 56 and at slaughter(80 d) to determine circulating plasma leptin. Samples of Longissimus dorsi were taken at slaughter for leptin gene expression levels.Results: DMI and RFI were different between groups and LRFI animals showed less back fat and rump fat thickness,as well as less pelvic and kidney fat weight. Circulating leptin increased over time in all animals. Plasma leptin was greater in LRFI on 56 d and at slaughter(P = 0.0049). Gene expression of leptin were greater in LRFI animals(P = 0.0022) in accordance with the plasma levels. The animals of the LRFI group were leaner, ate less, and had more circulating leptin and its gene expression.Conclusion: These findings demonstrated that leptin plays its physiological role in young Nellore bulls, probably controlling food intake because feed efficient animals have more leptin and lower residual feed intake.

Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size,and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor(FXR)and the G-protein-coupled bile acid receptor(TGR5).

Leptin in normal physiology and leptin resistance

自从1994年瘦素作为一个脂肪细胞因子被发现,关于瘦素的研究已经取得了很多进展.瘦素与瘦素受体的结合,在中枢神经系统,特别是在下丘脑中激活STAT3依赖和非依赖的信号通路、在维持能量稳态、神经内分泌作用和代谢等方面都发挥了很重要的作用.瘦素抵抗是肥胖的一个重要危险因素.目前提出的引起瘦素抵抗的机制主要包括瘦素运输受损、瘦素信号通路削弱、内质网应激、炎症和自噬缺陷.在此,我们对瘦素的功能、瘦素的信号通路,以及瘦素抵抗等进行了综述,希望可以为对抗肥胖的研究提供新的思路.

Intercellular and inter-organ crosstalk in browning of white adipose tissue:molecular mechanism and therapeutic complications

Adipose tissue(AT)is highly plastic and heterogeneous in response to environmental and nutritional changes.The development of heat-dissipating beige adipocytes in white AT(WAT)through a process known as browning(or beiging)has garnered much attention as a promising therapeutic strategy for obesity and its related metabolic complications.This is due to its inducibility in response to thermogenic stimulation and its association with improved metabolic health.WAT consists of adipocytes,nerves,vascular endothelial cells,various types of immune cells,adipocyte progenitor cells,and fibroblasts.These cells contribute to the formation of beige adipocytes through the release of protein factors that significantly influence browning capacity.In addition,inter-organ crosstalk is also important for beige adipocyte biogenesis.Here,we summarize recent findings on fat depot-specific differences,secretory factors participating in intercellular and inter-organ communications that regulate the recruitment of thermogenic beige adipocytes,as well as challenges in targeting beige adipocytes as a potential anti-obese therapy.

Aberrations of biochemical indicators in amyotrophic lateral sclerosis:a systematic review and meta-analysis

Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis(ALS)are not only confined to the central nervous system but also occur in the peripheral circulating system.Here,we performed a meta-analysis based on the PubMed,EMBASE,EBSCO,and CNKI databases,to find out biochemical indicators associated with energy metabolism,iron homeostasis,and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes.Forty-six studies covering 17 biochemical indicators,representing 5454 ALS patients and 7986 control subjects,were included in this meta-analysis.Four indicators,including fasting blood glucose level(weighted mean difference[WMD]=0.13,95%CI[0.06-0.21],P=0.001),serum ferritin level(WMD=63.42,95%CI[48.12-78.73],P<0.001),transferrin saturation coefficient level(WMD=2.79,95%CI[1.52-4.05],P<0.001),and creatine kinase level(WMD=80.29,95%CI[32.90-127.67],P<0.001),were significantly higher in the ALS patients,whereas the total iron-binding capacity(WMD=-2.42,95%CI[-3.93,-0.90],P=0.002)was significantly lower in ALS patients than in the control subjects.In contrast,the other 12 candidates did not show significant differences between ALS patients and controls.Moreover,pooled hazard ratios(HR)showed significantly reduced survival(HR=1.38,95%CI[1.02-1.88],P=0.039)of ALS patients with elevated serum ferritin levels.These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS.In addition,the serum ferritin level is negatively associated with the overall survival of ALS patients.

Metabolic actions of FGF21:molecular mechanisms and therapeutic implications

Fibroblast growth factor 21(FGF21)is an atypical member of the FGF family that functions as an endocrine factor.In obese animals,elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight,decreases hyperglycemia and hyperlipidemia,alleviates fatty liver and increases insulin sensitivity.FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets,including adipose tissue,liver,brain and pancreas.The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma(PPARγ)and peroxisome proliferator.-activated receptor alpha(PPARα).A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21.In humans,plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes,but are reduced in patients with autoimmune diabetes.This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions,and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.