Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences ...of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells.
Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. For the physiological studies, mice carrying ablation of GHR exclusively in ChAT-expressing cells were produced and possible changes in energy and glucose homeostasis were determined when consuming regular chow or high-fat diet (HFD).
The majority of cholinergic neurons in the arcuate nucleus (60%) and dorsomedial nucleus (84%) of the hypothalamus are directly responsive to GH. Approximately 34% of pre-ganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus also exhibited GH-induced pSTAT5. GH-induced pSTAT5 in these ChAT neurons was absent in GHR ChAT knockout mice. Mice carrying ChAT-specific GHR deletion, either in chow or HFD, did not exhibit significant changes in body weight, body adiposity, lean body mass, food intake, energy expenditure, respiratory quotient, ambulatory activity, serum leptin levels, glucose tolerance, insulin sensitivity and metabolic responses to 2-deoxy-d-glucose. However, GHR deletion in ChAT neurons caused decreased hypothalamic Pomc mRNA levels in HFD mice.
Cholinergic neurons that regulate the metabolism are directly responsive to GH, although GHR signaling in these cells is not required for energy and glucose homeostasis. Thus, the physiological importance of GH action on cholinergic neurons still needs to be identified.
Thiazolidinediones (TZDs) enhanced body weight (BW) partially by increased adipogenesis and hyperphagia. Neuronal PPARγ knockout mice on high-fat diet (HFD) are leaner because of enhanced leptin ...response, although it could be secondary to their leanness. Thus, it still is an open question how TZDs may alter energy balance. Multiple factors regulate food intake (FI) and energy expenditure (EE), including anorexigenic hormones as insulin and leptin. Nonetheless, elevated hypothalamic AMPK activity increases FI and TZDs increase AMPK activity in muscle cells. Thus, the aim of the present study was to investigate whether Pioglitazone (PIO) treatment alters hypothalamic insulin and leptin action/signaling, AMPK phosphorylation, and whether these alterations may be implicated in the regulation of FI and EE.
Swiss mice on HFD (2 months) received PIO (25 mg kg(-1) per day-gavage) or vehicle for 14 days. AMPK and AdipoR1 were inhibited via Intracerebroventricular injections using Compound C (CompC) and small interference RNA (siRNA), respectively. Western blot, real-time PCR and CLAMS were done.
PIO treatment increased BW, adiposity, FI, NPY mRNA and decreased POMC mRNA expression and EE in HFD mice. Despite higher adiposity, PIO treatment improved insulin sensitivity, glucose tolerance, decreased insulin and increased adiponectin serum levels. This result was associated with, improved insulin and leptin action/signaling, decreased α2AMPK(Ser491) phosphorylation and elevated Acetyl-CoA carboxylase and AMPK(Thr172) phosphorylation in hypothalamus. The inhibition of hypothalamic AMPK with CompC was associated with decreased adiposity, FI, NPY mRNA and EE in PIO-treated mice. The reduced expression of hypothalamic AdipoR1 with siRNA concomitantly with PIO treatment reverted PIO induced obesity development, suggesting that adiponectin may be involved in this effect.
These results demonstrated that PIO, despite improving insulin/leptin action in hypothalamus, increases FI and decreases EE, partially, by activating hypothalamic adiponectin/AdipoR1/AMPK axis. Suggesting a novel mechanism in the hypothalamus by which TZDs increase BW.
To investigate whether the Cdc2-like kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance.
Swiss mice on ...chow or high-fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus.
Hypothalamic CLK2
phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K (phosphoinositide 3-kinase)-dependent manner. The reduction of CLK2 expression in the hypothalamus, by chronic pharmacological inhibition with TG003 or by chronic knockdown with small interfering RNA was sufficient to abolish the anorexigenic effect of insulin and leptin, to increase body weight, fat mass, food intake and to decrease energy expenditure in mice on chow. In contrast, CLK2
phosphorylation in the hypothalamus in response to insulin, leptin or refeeding was impaired in mice on HFD or in db/db mice. Chronic CLK2 inhibition in the hypothalamus was associated with a slight increase in the fasting blood glucose levels, reduction in PEPCK (phosphoenolpyruvate carboxykinase) expression in the liver and enhanced glucose production from pyruvate, suggesting a regulation of hepatic glucose production. Further, overexpressing CLK2 in the mediobasal hypothalami of mice on HFD or in db/db mice by adenovirus partially reversed the obese phenotype.
Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.
The mallard duck or wild duck (Anas platyrhynchos) is the world's most widespread and numerous dabbling duck, being traditionally hunted across many countries in Europe and North America. This study ...aims to provide a detailed characterization of mallard duck's meat lipid fraction obtained from farmed specimens, reared for hunting purposes, under semiextensive conditions. The mallard's duck meat total lipid content averaged 2.0 and 4.26 g/100 g of fresh meat in breast and leg meat portions, and its meat comprised 23 individual fatty acids (FA) and 3 dimethylacetals (DMA), independently of the sex or meat portion. The oleic (C18:1 cis-9), palmitic (C16:0), stearic (C18:0), linoleic (C18:2n-6), arachidonic (C20:4n-6), palmitoleic (C16:1 cis-9), and cis-vaccenic (C18:1 cis-11) acids were the predominant FA (representing >1% of total fatty acids in both breast and leg meat portions and independently of the sex), and together, these 7 fatty acids were accountable for 92.4 to 96.5% of total FA plus DMA in mallard duck meat. The monounsaturated, saturated and polyunsaturated fatty acids were accountable for 40.4, 35.0, and 21.0% of total FA plus DMA in breast and 54.6, 38.7, and 5.7% of total fatty acids in leg, while total DMA were liable for 3.6 and 0.9% of total FA plus DMA in breast and leg, respectively. The mallard duck meat total cholesterol content averaged 49.8 and 57.1 mg/100 g of fresh meat for breast and leg meat portions. Five tocochromanols were quantified in mallard duck meat, affording it with a total vitamin E content of 5.48 and 3.63 µg/g of fresh meat in breast and leg portions.
The sex had no influence (P > 0.05) on mallard's duck meat lipid composition, but meat portion had a strong influence on mallard's duck meat lipid composition, influencing total lipid, total cholesterol, total vitamin E contents, FA partial sums, FA ratios (exception made for the n-6/n-3 ratio), and all nutritional lipid indices. The breast meat presented lower total lipid and total cholesterol contents, better FA ratios and nutritional quality indices and higher vitamin E content, being regarded as a healthier meat than leg. The study presented herein shows that mallard duck production in semiextensive conditions, similar to those used herein, could be used for the production of mallard duck beyond hunting. A production of duck's meat under natural or organic production practices, oriented to a market niche within the gourmet/organic markets.
The dissemination of carbapenem-resistant and third generation cephalosporin-resistant pathogens is a critical issue that is no longer restricted to hospital settings. The rapid spread of critical ...priority pathogens in Brazil is notably worrying, considering its continental dimension, the diversity of international trade, livestock production, and human travel. We conducted a nationwide genomic investigation under a One Health perspective that included Escherichia coli strains isolated from humans and nonhuman sources, over 45 years (1974-2019). One hundred sixty-seven genomes were analyzed extracting clinically relevant information (i.e., resistome, virulome, mobilome, sequence types STs, and phylogenomic). The endemic status of extended-spectrum β-lactamase (ESBL)-positive strains carrying a wide diversity of
variants, and the growing number of colistin-resistant isolates carrying
-type genes was associated with the successful expansion of international ST10, ST38, ST115, ST131, ST354, ST410, ST648, ST517, and ST711 clones; phylogenetically related and shared between human and nonhuman hosts, and polluted aquatic environments. Otherwise, carbapenem-resistant ST48, ST90, ST155, ST167, ST224, ST349, ST457, ST648, ST707, ST744, ST774, and ST2509 clones from human host harbored
and
genes. A broad resistome to other clinically relevant antibiotics, hazardous heavy metals, disinfectants, and pesticides was further predicted. Wide virulome associated with invasion/adherence, exotoxin and siderophore production was related to phylogroup B2. The convergence of wide resistome and virulome has contributed to the persistence and rapid spread of international high-risk clones of critical priority E. coli at the human-animal-environmental interface, which must be considered a One Health challenge for a post-pandemic scenario.
A One Health approach for antimicrobial resistance must integrate whole-genome sequencing surveillance data of critical priority pathogens from human, animal and environmental sources to track hot spots and routes of transmission and developing effective prevention and control strategies. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we present genomic data of WHO critical priority carbapenemase-resistant, ESBL-producing, and/or colistin-resistant Escherichia coli strains isolated from humans and nonhuman sources in Brazil, a country with continental proportions and high levels of antimicrobial resistance. The present study provided evidence of epidemiological and clinical interest, highlighting that the convergence of wide virulome and resistome has contributed to the persistence and rapid spread of international high-risk clones of E. coli at the human-animal-environmental interface, which must be considered a One Health threat that requires coordinated actions to reduce its incidence in humans and nonhuman hosts.
Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, ...histopathological and immunohistochemical findings in livers of squirrel monkeys (
spp.) infected with the YFV. Viremia occurred 1-30 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-γ and TNF-α, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease.
This study evaluates both the occurrence and removal of 24 compounds, including drugs and endocrine disruptors, in 8 water treatment plants (WTP) located in the metropolitan region of Belo Horizonte ...(Minas Gerais State, Brazil). The compounds 4-nonylphenol, 4-octylphenol, 17α-ethinylestradiol, 17β-estradiol, acyclovir, bisphenol A, bezafibrate, caffeine, dexamethasone, diclofenac sodium, diltiazem, estrone, estriol, gemfibrozil, ibuprofen, linezolid, loratadine, losartan, metformin, naproxen, paracetamol, promethazine, propranolol and sulfamethoxazole were monitored at 3 sampling points (raw water, filtered water, treated water) over 10 or 12 collection campaigns for each WTP. The results showed that bisphenol A occurred at higher concentrations during the dry period with a maximum concentration of 3257.1 ng L
−1
, while the compounds 4-nonylphenol and losartan exhibited higher concentrations in the rainy period with maximum concentrations of 8577.2 ng L
−1
and 705.8 ng L
−1
, respectively. Regarding the removal of compounds in the monitored WTPs, the clarification step demonstrated better removals for 4-nonylphenol, bisphenol-A, paracetamol, and sulfamethoxazole, whereas the disinfection step mainly removed the compounds 4-octylphenol and estrone. Margin of exposure (ME) assessment results indicated that only dexamethasone, ethinyl estradiol, diclofenac, estradiol, and estrone were classified as imminent risk or alert considering the 95th percentile concentration found in the samples of treated water.
Caponization is associated with some morbidity and mortality, which contributes to important economic losses. This practice is executed without any pain relief (neither anesthesia nor analgesia) and ...can be painful and without consideration of animal welfare. On the other hand, immunocastration accomplished by Improvac and Bovipriva in pigs and cattle represents a noninvasive procedure, and for that reason is regarded as an alternative with improved animal welfare. This study includes 4 experimental groups consisting of capons, slips, roosters, and birds submitted to the Improvac treatment. The administration of Improvac was associated with a considerable reduction in serum testosterone concentration (reduced by 79% compared to average serum testosterone of roosters). Regarding significant differences among experimental groups, birds from the Improvac group were intermediate between capons and slips with respect to abdominal fat pad weight and yield, breast meat water and protein contents, and femur length. Conversely, color parameters such as lightness, redness, and hue angle for Improvac birds were intermediate between roosters and capons. Thus, immunocastration with Improvac could represent an alternative solution to caponization, with considerable improvements in animal welfare.
Recently, immunocastration with Improvac (ImmC). has been tested in broilers and a considerable reduction in serum testosterone concentration (reduced by 79% compared to roosters) was observed. The ...aim of this study was to evaluate the effect of immunocastration on meat fatty acid (FA) composition and its comparison with caponized and intact males (roosters). The study was conducted with 3 experimental groups: control group (roosters), the group of birds submitted to surgical caponization (SurgC), and the group of birds submitted to immunocastration with Improvac. The comparison of breast meat partial FA sums of castrated (SurgC and ImmC) with control birds (roosters) revealed that castrated birds showed significantly higher content of n-3 polyunsaturated fatty acids (n-3 PUFA) than control birds (1.76 vs. 1.46 g/100 g of total FA; superiority of 20.2%), which has contributed to the occurrence of significant differences on both the n-6/n-3 ratio and the atherogenicity index (AI). In contrast, on leg meat portion, castrated birds displayed higher contents of both total saturated and monounsaturated fatty acids (SFA and MUFA, with 2.2 and 4.1% more, respectively) and lower total n-6 PUFA content (8.3% less) than was observed in control birds, which contributed to significant differences in the AI index. On the other hand, the comparison of breast meat portion from SurgC with ImmC showed that immunocastration contributed to lower total SFA and higher total n-6 PUFA, which have contributed to significant differences on both Polyunsaturated/Saturated (P/S) and n-6/n-3 ratios. Whereas, on leg meat portion no significant differences were observed on partial sums and a single difference was observed on the thrombogenicity index. Immunocastration of broilers has contributed to minor changes in the FA profile, but has improved the overall lipid quality indexes in both breast and leg meat portions. Therefore, immunocastration could be applied as an alternative method to caponization without negative consequences in meat FA profile.
Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised ...protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise.
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