Control Of Energy Balance Research Articles

12502 Bdnf Production by Kiss1 Neurons Acts in a Sexually Dependent Way to Control Sexual Development and Energy Balance in Female and Male Mice

Abstract Disclosure: A.M. Zanesco: None. D. Cabral: None. J. Ferreira: None. F. Valdivieso-Rivera: None. A.L. Carvalho: None. N. Mendes: None. C. Sponton: None. R. Frazao: None. L.A. Velloso: None. The hypothalamus is a key region in the central nervous system that controls different functions such as energy balance, thermogenesis, and reproduction. Kiss1 neurons integrate two distinct neuronal pathways, reproduction, and energy balance, both essential to species survival and maintenance. Recent studies, identify that the Brain-derived neurotrophic factor, BDNF produced by neurons and astrocytes in the hypothalamus is essential to control homeostatic and hedonic feeding by acting in specific groups of hypothalamic neurons. No studies showed the action of BDNF produced in the arcuate nucleus (ARC) of the hypothalamus. Using single-cell RNA sequencing analysis of data obtained from mice hypothalamus reveals that Kiss1 neurons express BDNF and we confirmed this result by immunofluorescence assay. Curiously, there is more expression of BDNF in the female hypothalamus compared with the male hypothalamus. But, when we selected specifically the BDNF produced by KISS1 neurons, this difference disappears. Based on that, we used a Cre-loxP approach to selectively knockout BDNF in Kiss1 neurons and identify the changes in sexual development and energy balance in female and male mice. All experiments were approved by the Animal Use Ethics Committee of UNICAMP (CEUA: 5591-1/2020 and CIBio 04/2021). All female and male mice were evaluated daily to identify their sexual development. We identified no changes in metabolic parameters, such as body weight and adiposity in male and female mice fed on a chow diet. Additionally, BDNF ablation in Kiss1 neurons (BDNF-KO) leaded to a premature vaginal opening, a decreased in uterus and ovary weight, and compromises the regular cyclicity of the estrus cycle in females. No difference was found in the sexual development of male mice, indicating that this effect is sexually dependent. Based on the fact that BDNF produced in VMH and DMH acts as anorexigenic effects, and Kiss1 neurons integrate the neuronal pathway responsible for energy balance, we decided to investigate the effects of BDNF ablation in Kiss1 neurons in female and male mice fed on high-fat diet. Interestingly, male mice without BDNF production in Kiss neurons were protected from obesity development compared with wild-type mice, both fed on a high-fat diet. When they were fed on a chow diet, male BDNF-KO mice, exhibited hyperphagia compared to control mice, showing a disruption in control of food intake and body weight maintenance. No differences were identified in body weight gain, food intake, and adiposity in BDNF-KO female mice. Based on that, we conclude that BDNF produced by Kiss1 exerts different functions in male and female mice. In females, it is more related to sexual development, and males in control of energy balance. This is the first research showing the BDNF production by Kiss1 neurons and its dimorphism effects on male and female mice. Presentation: 6/2/2024

8369 Overexpression of Neurosecretory Protein GL, a Novel Small Secretory Protein, Induces Fat Accumulation in Mice

Abstract Disclosure: K. Ukena: None. Y. Narimatsu: None. A. Ogasawara: None. M. Furumitsu: None. E. Iwakoshi-Ukena: None. Hypothalamic neuropeptides and peripheral factors influence food intake, body mass, and energy expenditure. For instance, neuropeptide Y (NPY)/agouti-related peptide (AgRP) are potent orexigenic factors and α-melanocyte-stimulating hormone (α-MSH) is an anorexigenic factor, respectively. In addition, leptin and insulin derived from peripheral tissues act on the hypothalamus to influence energy homeostasis. Precise hypothalamic control of energy balance affects puberty, thermoregulation, energy storage, and survival during different life-history stages. We have previously discovered a novel cDNA encoding the precursor of a neurosecretory small protein in the hypothalamus of birds and rodents (1, 2). The precursor protein contained a signal peptide sequence, a mature peptide sequence with 80 amino acid residues, a glycine amidation signal, and a dibasic amino acid cleavage site. Because the predicted C-terminal amino acids of the peptide were Gly-Leu-NH2, the small protein was named neurosecretory protein GL (NPGL). Quantitative RT-PCR analysis demonstrated that NPGL mRNA was expressed exclusively in the mediobasal hypothalamus (MBH), including the arcuate nucleus, and the expression was elevated on food deprivation in rodents. This finding led us to predict that NPGL was involved in the regulation of energy homeostasis. Indeed, using NPGL administration and neutralizing antibody administration in rats, we established that NPGL increased lipid accumulation in white adipose tissue (3). In the present study, to investigate the physiological function of NPGL in mice, we induced its overexpression using an adeno-associated virus (AAV) vector in NPGL-Cre driver mice. We then monitored food intake and recorded body mass changes. Npgl overexpression increased body mass. We also found that the overexpression resulted in increased masses of white adipose tissue and interscapular brown adipose tissue. Taken together, these results provide evidence for NPGL as a novel regulator of fat deposition in adipose tissues. Reference: (1) Ukena et al., Biochem. Biophys. Res. Commun. 2014 446:298-303. (2) Ukena, Gen. Comp. Endocrinol. 2018 260:164-170. (3) Iwakoshi-Ukena et al., eLife 2017 6:e28527. Presentation: 6/3/2024

Ventral tegmental area amylin / calcitonin receptor signaling suppresses feeding and weight gain in female rats

The pancreatic peptide amylin promotes negative energy balance in part through activation of amylin receptors (AmyRs) expressed in the ventral tegmental area (VTA), but studies have been limited to male rodents. We evaluated whether VTA amylin signaling governs feeding and body weight in female rats. Indeed, pharmacological VTA AmyR activation suppressed chow intake and body weight in females. Viral-mediated knockdown of VTA calcitonin receptor (GPCR of AmyR) supports the physiological relevance of VTA amylin signaling for energy balance control in females. Collectively, these data support the relevance of VTA amylin signaling for energy balance control in both sexes.

Angiotensin in the Arcuate: Mechanisms Integrating Cardiometabolic Control.

The American Heart Association has identified obesity as a primary impediment to ongoing improvements in cardiovascular diseases, including hypertension. Although drugs, exercise, diets, and surgeries can each cause weight loss, few subjects maintain a reduced weight over the long term. Dysfunctional integrative control (ie, adaptation) of resting metabolic rate (RMR) appears to underlie this failed weight maintenance, yet the neurobiology of physiological and pathophysiological RMR control is poorly understood. Recent insights into the cellular and molecular control of RMR by Ang-II (angiotensin II) signaling within the arcuate nucleus of the hypothalamus are reviewed. Within a unique subset of AgRP (agouti-related peptide) neurons, AT1Rs (Ang-II type 1 receptors) are implicated in the integrative control of RMR. Furthermore, a spontaneous G protein signal switch of AT1R within this neuron type appears to underlie the pathogenesis of RMR adaptation by qualitatively changing the cellular response to AT1R activation from a β-arrestin-1/Gαi-mediated inhibitory response to a Gαq-mediated stimulatory response. Therapeutic approaches to obesity are likely hampered by the plasticity of the signaling mechanisms that mediate the normal integrative control of energy balance. The same stimulus that would increase RMR in the normal physiological state may decrease RMR during obesity due to qualitative changes in second-messenger coupling. Understanding the mechanisms that regulate interactions between receptors such as AT1R and its various second-messenger signaling cascades will provide novel insights into the pathogenesis of RMR adaptation and potentially point toward new therapeutic approaches for obesity and hypertension.

Association between rs4994 variant in β3-Adrenergic receptor and obesity in Vietnamese preschool-age children, independent of eating behaviors

BackgroundThe Arg64 allele of the rs4994 (Trp64Arg) variant in the β3-adrenergic receptor (ADRB3) gene is involved in the control of energy balance by altering lipolysis and thermogenesis in adipocytes, ultimately contributing to the development of obesity. The objective of our study was to investigate the association between the rs4994 variant of the ADRB3 gene and obesity in Hanoi preschool-age children, adjusting for their eating behaviors.MethodsA cross-sectional study was performed involving 708 children with normal weight and 304 children with obesity aged 3–5 years from 36 kindergartens in Hanoi, Vietnam. Cheek mucosa cell samples were used for DNA extraction, and genotyping at the ADRB3-rs4994 locus was performed using the polymerase chain reaction–restriction fragment length polymorphism method (PCR–RFLP). Eating behaviors were assessed using the Children’s Eating Behaviour Questionnaire (CEBQ). Binary logistic regression analysis was employed to examine the association between the rs4994 variant and obesity, adjusting for confounding factors such as age, sex, residence, birth weight, and eating behaviors.ResultsThe frequency of the C allele in the group with obesity was 16.4%, which was higher than in the control group (11.7%, P = 0.003). Children with the CC genotype exhibited significantly greater weight and weight-for-age Z-score compared to those with the TT and TC genotypes (P = 0.004 and 0.03, respectively). Following univariate and multivariate analyses adjusted for age, sex, residence, birth weight, and eating behaviors, a significant association between the rs4994 variant and obesity was observed (P < 0.05).ConclusionsThis study indicated that the ADRB3-rs4994 variant can be considered as an independent risk factor for obesity in Vietnamese preschool children.

Fasting-induced activity changes in MC3R neurons of the paraventricular nucleus of the thalamus.

The brain controls energy homeostasis by regulating food intake through signaling within the melanocortin system. Whilst we understand the role of the hypothalamus within this system, how extra-hypothalamic brain regions are involved in controlling energy balance remains unclear. Here we show that the melanocortin 3 receptor (MC3R) is expressed in the paraventricular nucleus of the thalamus (PVT). We tested whether fasting would change the activity of MC3R neurons in this region by assessing the levels of c-Fos and pCREB as neuronal activity markers. We determined that overnight fasting causes a significant reduction in pCREB levels within PVT-MC3R neurons. We then questioned whether perturbation of MC3R signaling, during fasting, would result in altered refeeding. Using chemogenetic approaches, we show that modulation of MC3R activity, during the fasting period, does not impact body weight regain or total food intake in the refeeding period. However, we did observe significant differences in the pattern of feeding-related behavior. These findings suggest that the PVT is a region where MC3R neurons respond to energy deprivation and modulate refeeding behavior.

SOC and SOH state estimation of lithium battery based on ffrls and kalman filter

Abstract In the energy storage System, the Battery Management System (BMS) is responsible for the charge and discharge control and energy balance control of the lithium battery, and the accuracy of lithium battery state estimation is directly affected by the control effect of BMS. In order to ensure the normal operation of lithium batteries, this paper selects the State of Charge (SOC) and State of Health (SOH) of lithium batteries as the research object and accurately estimates the SOC and SOH of lithium batteries as the research goal. The equivalent circuit model based on lithium battery is established, and the identification model parameters are based on the recursive least squares method with forgetting factor. Based on the Thevenin equivalent circuit model, the Extended Kalman Filter (EKF) and Unscented Kalman Filter (UKF) are used to estimate the SOC of the battery, respectively. FFRLS and Double Extended Kalman Filter (DEKF) are used to estimate the ohm internal resistance in the equivalent model based on lithium battery, and then the SOH is estimated.

Advancements in Utilizing Natural Compounds for Modulating Autophagy in Liver Cancer: Molecular Mechanisms and Therapeutic Targets.

Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.

Chemogenetic Excitation of Ventromedial Hypothalamic Steroidogenic Factor 1 (SF1) Neurons Increases Muscle Thermogenesis in Mice.

Allostatic adaptations to a perceived threat are crucial for survival and may tap into mechanisms serving the homeostatic control of energy balance. We previously established that exposure to predator odor (PO) in rats significantly increases skeletal muscle thermogenesis and energy expenditure (EE). Evidence highlights steroidogenic factor 1 (SF1) cells within the central and dorsomedial ventromedial hypothalamus (c/dmVMH) as a modulator of both energy homeostasis and defensive behavior. However, the brain mechanism driving elevated EE and muscle thermogenesis during PO exposure has yet to be elucidated. To assess the ability of SF1 neurons of the c/dmVMH to induce muscle thermogenesis, we used the combined technology of chemogenetics, transgenic mice, temperature transponders, and indirect calorimetry. Here, we evaluate EE and muscle thermogenesis in SF1-Cre mice exposed to PO (ferret odor) compared to transgenic and viral controls. We detected significant increases in muscle temperature, EE, and oxygen consumption following the chemogenetic stimulation of SF1 cells. However, there were no detectable changes in muscle temperature in response to PO in either the presence or absence of chemogenetic stimulation. While the specific role of the VMH SF1 cells in PO-induced thermogenesis remains uncertain, these data establish a supporting role for SF1 neurons in the induction of muscle thermogenesis and EE similar to what is seen after predator threats.

AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation.

Hypothalamic neural circuits maintain homeostasis by coordinating endocrine signals with autonomic responses and behavioral outputs to ensure that physiological responses remain in tune with environmental demands. The paraventricular nucleus of the hypothalamus (PVH) plays a central role in metabolic regulation, and the architecture of its neural inputs and axonal projections is a defining feature of how it receives and conveys neuroendocrine information. In adults, leptin regulates multiple aspects of metabolic physiology, but it also functions during development to direct formation of circuits controlling homeostatic functions. Here we demonstrate that leptin acts to specify the input-output architecture of PVH circuits through an activity-dependent, transsynaptic mechanism, which represents a novel means of sculpting neuroendocrine circuitry, with lasting effects on how the brain controls energy balance.

Reductions of food intake and body weight in diet-induced obese rats following chronic treatment with a monomeric peptide multiagonist

While therapies based on endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have been compelling therapeutic agents for obesity and type 2 diabetes (T2D), only a few have achieved long-term weight loss and all have shown significant side-effects, including nausea/malaise and gastrointestinal ailments. As the pathophysiology of obesity is driven by dysregulation of multiple, inter-related, pathways, we tested a novel peptide targeting multiple receptors of complementary neurocircuits regulating the controls of energy balance. Response to daily injections of GEP44, a GLP-1R and neuropeptide Y1R and Y2R receptor (Y1R/Y2R) triple agonist was tested vs. the GLP-1R agonist liraglutide (LIRA) in diet-induced obese (DIO) male and female rats. Glucose tolerance tests after intraperitoneal injection of glucose (IPGTT) were performed at baseline and after 14-d of treatment in GEP44 treated rats. Other metabolic parameters were assessed in blood at the end of a 28-d intervention. Upon conclusion at 28-d, body weight reduction compared to vehicle was-15.6%/-11.9% in response to GEP44, vs.-9.7%/-5.1% after LIRA, males, and females, respectively. Significant reductions of cumulative food intake occurred over 28-d in female rats treated with GEP44 (-30%; p<0.0001), vs. LIRA (-10%), and in male rats GEP44 (-39%; p<0.0001), vs. LIRA (-20%; p=0.003). In IPGTTs, a similar stimulation glucose induced insulin secretion was noted in rats treated with GEP44 and LIRA. The strong reductions of body weight in response to long-term applications of the triple agonist GEP44 confirms the therapeutic potential of targeting multiple receptors for achieving more robust and potentially more sustained improvement of energy balance.

Ventromedial hypothalamic nucleus subset stimulates tissue thermogenesis via preoptic area outputs

ObjectiveHypothalamic signals potently stimulate energy expenditure by engaging peripheral mechanisms to restore energy homeostasis. Previous studies have identified several critical hypothalamic sites (e.g. preoptic area (POA) and ventromedial hypothalamic nucleus (VMN)) that could be part of an interconnected neurocircuit that controls tissue thermogenesis and essential for body weight control. However, the key neurocircuit that can stimulate energy expenditure has not yet been established. MethodsHere, we investigated the downstream mechanisms by which VMN neurons stimulate adipose tissue thermogenesis. We manipulated subsets of VMN neurons acutely as well as chronically and studied its effect on tissue thermogenesis and body weight control, using Sf1Cre and Adcyap1Cre mice and measured physiological parameters under both high-fat diet and standard chow diet conditions. To determine the node efferent to these VMN neurons, that is involved in modulating energy expenditure, we employed electrophysiology and optogenetics experiments combined with measurements using tissue-implantable temperature microchips. ResultsActivation of the VMN neurons that express the steroidogenic factor 1 (Sf1; VMNSf1 neurons) reduced body weight, adiposity and increased energy expenditure in diet-induced obese mice. This function is likely mediated, at least in part, by the release of the pituitary adenylate cyclase-activating polypeptide (PACAP; encoded by the Adcyap1 gene) by the VMN neurons, since we previously demonstrated that PACAP, at the VMN, plays a key role in energy expenditure control. Thus, we then shifted focus to the subpopulation of VMNSf1 neurons that contain the neuropeptide PACAP (VMNPACAP neurons). Since the VMN neurons do not directly project to the peripheral tissues, we traced the location of the VMNPACAP neurons' efferents. We identified that VMNPACAP neurons project to and activate neurons in the caudal regions of the POA whereby these projections stimulate tissue thermogenesis in brown and beige adipose tissue. We demonstrated that selective activation of caudal POA projections from VMNPACAP neurons induces tissue thermogenesis, most potently in negative energy balance and activating these projections lead to some similar, but mostly unique, patterns of gene expression in brown and beige tissue. Finally, we demonstrated that the activation of the VMNPACAP neurons' efferents that lie at the caudal POA are necessary for inducing tissue thermogenesis in brown and beige adipose tissue. ConclusionsThese data indicate that VMNPACAP connections with the caudal POA neurons impact adipose tissue function and are important for induction of tissue thermogenesis. Our data suggests that the VMNPACAP → caudal POA neurocircuit and its components are critical for controlling energy balance by activating energy expenditure and body weight control.

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor

Introduction: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown. Methods: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder. Results: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens. Discussion: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.

Neuroactive steroids in the neuroendocrine control of food intake, metabolism, and reproduction.

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids.

Multiple metabolic signals in the CeA regulate feeding: The role of AMPK

BackgroundThe central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and controls energy balance. Recently, a cluster of neurons was identified as responsive to the orexigenic effect of ghrelin and fasting. However, the signaling pathway by which ghrelin and fasting induce feeding is unknown. AMP-activated protein kinase (AMPK) is a cellular energy sensor, and its Thr172 phosphorylation (AMPKThr172) in the mediobasal hypothalamus regulates food intake. However, whether the expression and activation of AMPK in CeA could be one of the intracellular signaling activated in response to ghrelin and fasting eliciting food intake is unknown. AimTo evaluate the activation of AMPK into CeA in response to ghrelin, fasting, and 2-deoxy-D-glucose (2DG) and whether feeding accompanied these changes. In addition, to investigate whether the inhibition of AMPK into CeA could decrease food intake. MethodsOn a chow diet, eight-week-old Wistar male rats were stereotaxically implanted with a cannula in the CeA to inject several modulators of AMPKα1/2Thr172 phosphorylation, and we performed physiological and molecular assays. Key findingsFasting increased, and refeeding reduced AMPKThr172 in the CeA. Intra-CeA glucose injection decreased feeding, whereas injection of 2DG, a glucoprivation inductor, in the CeA, increased food intake and blood glucose, despite faint increases in AMPKThr172. Intra-CeA ghrelin injection increased food intake and AMPKThr172. To further confirm the role of AMPK in the CeA, chronic injection of Melanotan II (MTII) in CeA reduced body mass and food intake over seven days together with a slight decrease in AMPKThr172. SignificanceOur findings identified that AMPK might be part of the signaling machinery in the CeA, which responds to nutrients and hormones contributing to feeding control. The results can contribute to understanding the pathophysiological mechanisms of altered feeding behavior/consumption, such as binge eating of caloric-dense, palatable food.

The Role of BDNF and TrkB in the Central Control of Energy and Glucose Balance: An Update.

The global rise in obesity and related health issues, such as type 2 diabetes and cardiovascular disease, is alarming. Gaining a deeper insight into the central neural pathways and mechanisms that regulate energy and glucose homeostasis is crucial for developing effective interventions to combat this debilitating condition. A significant body of evidence from studies in humans and rodents indicates that brain-derived neurotrophic factor (BDNF) signaling plays a key role in regulating feeding, energy expenditure, and glycemic control. BDNF is a highly conserved neurotrophin that signals via the tropomyosin-related kinase B (TrkB) receptor to facilitate neuronal survival, differentiation, and synaptic plasticity and function. Recent studies have shed light on the mechanisms through which BDNF influences energy and glucose balance. This review will cover our current understanding of the brain regions, neural circuits, and cellular and molecular mechanisms underlying the metabolic actions of BDNF and TrkB.

Abstract 1234 PTER controls energy balance via bidirectional taurine N-acetylation/hydrolysis

Abstract 1234 PTER controls energy balance via bidirectional taurine N-acetylation/hydrolysis

Prolactin Mediates Long-Term, Seasonal Rheostatic Regulation of Body Mass in Female Mammals.

A series of well-described anabolic and catabolic neuropeptides are known to provide short-term, homeostatic control of energy balance. The mechanisms that govern long-term, rheostatic control of regulated changes in energy balance are less well characterized. Using the robust and repeatable seasonal changes in body mass observed in Siberian hamsters, this report examined the role of prolactin in providing long-term rheostatic control of body mass and photoinduced changes in organ mass (ie, kidney, brown adipose tissue, uterine, and spleen). Endogenous circannual interval timing was observed after 4 months in a short photoperiod, indicated by a significant increase in body mass and prolactin mRNA expression in the pituitary gland. There was an inverse relationship between body mass and the expression of somatostatin (Sst) and cocaine- and amphetamine-regulated transcript (Cart). Pharmacological inhibition of prolactin release (via bromocriptine injection), reduced body mass of animals maintained in long photoperiods to winter-short photoperiod levels and was associated with a significant increase in hypothalamic Cart expression. Administration of ovine prolactin significantly increased body mass 24 hours after a single injection and the effect persisted after 3 consecutive daily injections. The data indicate that prolactin has pleiotropic effects on homeostatic sensors of energy balance (ie, Cart) and physiological effectors (ie, kidney, BAT). We propose that prolactin release from the pituitary gland acts as an output signal of the hypothalamic rheostat controller to regulate adaptive changes in body mass.

A Discrete-Time Current Control Method for the High-Speed Permanent Magnet Motor Drive Using the Modular Multilevel Converter

High-speed permanent magnet motors (HSPMMs) have received attention in direct drive systems from the industry. Modular multilevel converters (MMCs) have become the most practical solution for HSPMMs in industrial applications due to the advantages of their highly modular structure, high-quality output and high reliability. In this article, the symmetrical discrete-time model of the MMC for the HSPMM drive is presented. Based on this symmetrical discrete-time model, the discrete-time current regulator has been designed. Moreover, the submodel (SM) capacitor energy balance models for MMC have been described, and the energy balance control scheme is introduced. Finally, the simulation and experimental results show that the presented discrete-time current regulator has a strong dynamic response at high speed (15 kr/min), and the SM capacitor voltage balance control is also achieved. Compared with the conventional PI current controller, the proposed discrete-time current regulator improves the current loop dynamic performance at high-speed, and the energy balance control scheme can ensure the SM capacitor voltage balance of the MMC.

Association of fat mass and obesity associate (FTO) single nucleotide polymorphisms in the first intron and obesity risk among Indonesians

Obesity is one of the global pandemics characterized by an excessive fat buildup due to disruption of energy homeostasis in the body. As obesity is a risk factor for many other non-communicable diseases such as diabetes and coronary heart disease, it is crucial to understand the risk factors that contribute to the pathogenesis of obesity. Although obesity is mainly caused due to unhealthy lifestyles, genetic predisposition also plays a part in the pathogenesis of obesity. Individuals who carry risk alleles for genes that control energy balance in the body have a greater risk of developing obesity. Fat mass and obesity associate (FTO) is a gene strongly correlated with obesity and is widely expressed in the hypothalamus. This gene is predicted to have 89 common variations that affect obesity-related phenotypes. Among Indonesians, the three most studied single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene are rs1421085, rs17817449, and rs9939609. They are strongly associated with obesity’s related traits such as weight gain, fat mass, body mass index (BMI), waist, and hip sizes. rs993609 is the most studied among diverse ethnicities in Indonesia, with AA genotype and allele A as a risk allele.