scholarly journals The hypothalamus to brainstem circuit suppresses late-onset body weight gain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuko Maejima ◽  
Shigeki Kato ◽  
Shoichiro Horita ◽  
Yoichi Ueta ◽  
Seiichi Takenoshita ◽  
...  

AbstractBody weight (BW) is regulated in age-dependent manner; it continues to increase during growth period, and reaches a plateau once reaching adulthood. However, its underlying mechanism remains unknown. Regarding such mechanisms in the brain, we here report that neural circuits from the hypothalamus (paraventricular nucleus: PVN) to the brainstem (dorsal vagal complex: DVC) suppress late-onset BW gain without affecting food intake. The genetic suppression of the PVN-DVC circuit induced BW increase only in aged rats, indicating that this circuit contributes to suppress the BW at a fixed level after reaching adulthood. PVN neurons in the hypothalamus were inactive in younger rats but active in aged rats. The density of neuropeptide Y (NPY) terminal/fiber is reduced in the aged rat PVN area. The differences in neuronal activity, including oxytocin neurons in the PVN, were affected by the application of NPY or its receptor inhibitor, indicating that NPY is a possible regulator of this pathway. Our data provide new insights into understanding age-dependent BW regulation.

1999 ◽  
Vol 276 (6) ◽  
pp. R1617-R1622 ◽  
Author(s):  
David Michaud ◽  
Hymie Anisman ◽  
Zul Merali

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.


2010 ◽  
Vol 38 (4) ◽  
pp. 1001-1005 ◽  
Author(s):  
Kunie Ando ◽  
Karelle Leroy ◽  
Céline Heraud ◽  
Anna Kabova ◽  
Zehra Yilmaz ◽  
...  

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.


Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.


2008 ◽  
Vol 105 (6) ◽  
pp. 1695-1705 ◽  
Author(s):  
Parco M. Siu ◽  
Emidio E. Pistilli ◽  
Stephen E. Alway

Oxidative stress increases during unloading in muscle from young adult rats. The present study examined the markers of oxidative stress and antioxidant enzyme gene and protein expressions in medial gastrocnemius muscles of aged and young adult (30 and 6 mo of age) Fischer 344 × Brown Norway rats after 14 days of hindlimb suspension. Medial gastrocnemius muscle weight was decreased by ∼30% in young adult and aged rats following suspension. When muscle weight was normalized to animal body weight, it was reduced by 12% and 22% in young adult and aged rats, respectively, after suspension. Comparisons between young adult and aged control animals demonstrated a 25% and 51% decline in muscle mass when expressed as absolute muscle weight and muscle weight normalized to the animal body weight, respectively. H2O2 content was elevated by 43% while Mn superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended muscles compared with control muscles exclusively in the aged animals. Suspended muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE) (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine (76% and 65% increase in young adult and aged rats, respectively), and catalase activity (69% and 43% increase in young adult and aged rats, respectively) relative to control muscles. Changes in oxidative stress markers MDA/4-HAE, H2O2, and MnSOD protein contents in response to hindlimb unloading occurred in an age-dependent manner. These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia-associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading.


2019 ◽  
Vol 1 (3) ◽  
pp. 218-224 ◽  
Author(s):  
Andhika Putra ◽  
Wawan Setiawan Sinaga

Supplementation of cassava leaves (ManihotesculentaCrantz) in the base grass field ration of male rams in the growth period aims to determine the effect of giving cassava leaves to the performance of sheepparameters measured in this study were consumption level, body weight gain and feed conversion in local sheep in the growth period. This study used randomized complete design (CRD) 4 treatments and 6 replications. Using male local sheep with an average body weight of = 12 ± 1.93. The treatment used T0 = without giving cassava leaves (Control), T1 = 25% cassava leaves, T2 = 50% cassava leaves, T3 = 75% cassava leaves. The results of the study with variance analysis showed no significant effect (p> 0.05)feed consumption level, body weight gain and feed conversion ratio the conclusion of this study is the supplementation of cassava leaves (ManihotesculentaCrantz) on grass-based rations did not provide a different growth increase in weaning local male sheep.


2021 ◽  
Vol 12 ◽  
Author(s):  
Joice Cristina Kuchler ◽  
Bruna Schumaker Siqueira ◽  
Vanessa Marieli Ceglarek ◽  
Fernanda Vigilato Chasko ◽  
Isllany Carvalho Moura ◽  
...  

The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.


2018 ◽  
Vol 7 (2) ◽  
pp. 193-210
Author(s):  
Maria Victória Branco Flores ◽  
Tuany Eichwald ◽  
Analú Mantovani ◽  
Viviane Glaser ◽  
Carine Raquel Richter Schimitz ◽  
...  

O Manganês (Mn) é um metal essencial para o organismo. É distribuído no ambiente e utilizado em processos industriais. Apesar de essencial, é neurotóxico à exposições cumulativas, causando uma desordem neurológica, o Manganismo. O estudo avaliou o efeito da administração subaguda de Mn sob a forma de cloreto e acetato de Mn, sobre a função mitocondrial e parâmetros oxidativos no encéfalo, bem como o acúmulo deste metal no encéfalo e tecidos periféricos de ratos adultos. Os ratos receberam 6 mg/kg de Mn i.p. na forma de cloreto ou acetato de Mn, 5 dias/semana por 4 semanas. O grupo controle recebeu solução salina 0,9% pela mesma via de administração e mesmo período. Foi mensurada a concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS) e grupamentos NPSH, a atividade dos complexos I e II da cadeia respiratória no encéfalo e/ou estruturas cerebrais, bem como o peso corporal e a concentração de Mn e Fe no soro, encéfalo, tecido renal e hepático. Foi observada uma diminuição no ganho de peso corporal dos animais que receberam o Mn, um aumento na concentração/depósito de Mn no soro, encéfalo e tecido renal, tanto na forma de cloreto e acetato de Mn, quando comparados com o grupo controle. Além disso, houve um aumento significativo no conteúdo de NPSH no encéfalo e, embora não significativo, uma tendência de aumento da concentração de TBARS, no grupo que recebeu cloreto de Mn. Ainda, foi verificada uma inibição na atividade do complexo I no estriado dos animais expostos ao cloreto de Mn. Não houve diferença entre os grupos nas atividades do complexo I e II no encéfalo e hipocampo. Em conjunto, os dados indicam que a exposição ao Mn em baixas doses contribui para o desenvolvimento de estresse oxidativo e disfunção mitocondrial no SNC, com aparente predileção de dano ao estriado.Palavras-chave: Manganês. Exposição subaguda. Parâmetros oxidativos. Função mitocondrial. MANGANESE SUBACUTE INTOXICATION IN ADULT WISTAR RATS: EVALUATION OF OXIDATIVE PARAMETERS IN CNS AND METAL DEPOSITION IN DIFFERENT TISSUES ABSTRACT: Mn is an essential metal to the organism. It is distributed in the environment and used in industrial processes. Although essential, it is neurotoxic to cumulative exposures, and can cause a neurological disorder, called Manganism. This study evaluated the effect of subacute Mn as chloride and acetate of Mn administration on mitochondrial function and oxidative parameters in adult rat brain, as well as the accumulation of this metal in the brain and peripheral tissues. The rats received 6 mg/kg of Mn i.p., as Mn chloride or Mn acetate, 5 days/week for 4 weeks. The control group received 0.9% of saline solution in the same way of administration and in the same period. It was measured the concentration of thiobarbituric acid reactive substances (TBARS) and NPSH groups, the activity of mitochondrial complex I and II in brain and/or in the brain structures, as well as the body weight and the concentration of Mn and Fe accumulation. It was observed a decrease on body weight gain in animals exposed to Mn and an increase of concentration/deposit of Mn in serum, brain and kidney, in the both Mn chloride and acetate form when compared to the control group. In addition, there was a significant increase in brain NPSH content and, although it was not significant, a trend of increasing on TBARS concentration in the group that received Mn. Besides that, a significant inhibition of complex I activity was observed in the striatum of the animals exposed to Mn. There was not difference between groups on complex I and II in the brain and hippocampus. Together, these data indicate that exposure to Mn at low doses contributes to the development of oxidative stress and mitochondrial dysfunction in the CNS, with apparent predilection of striatum damage.Keywords: Manganese. Subacute exposure. Oxidative parameters. Mitochondrial function.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 129-129
Author(s):  
Meng Liu ◽  
Jin-Tao Wei ◽  
Kun-Tan Wu ◽  
Mahmoud Mohamed Khalil ◽  
Lv-hui Sun

Abstract This study was conducted to reveal the mechanism of T-2 toxin induced small intestine injuries in broilers through a new perspective that combined transcriptomics and microbiology studies. 96-d-old male Cobb broilers were randomly allocated into 4 treatment groups with 4 replicates of 6 birds/cage and all birds were fed a corn-soybean-based diet (Control) and the other 3 groups supplemented with T-2 toxin at 1.0, 3.0 or 6.0 mg/kg, respectively, for 2 weeks. Growth performance and nutrients digestibility were analyzed. Duodenum was collected to assay for histology, transcriptomics and microbiology. Compared with the control, final body weight, body weight gain and feed intake were decreased (P < 0.05) in a dose-dependent manner with increasing dietary T-2 toxin dose. Specially, in dietary T-2 toxin at 6.0 mg/kg, the feed/gain increased (P < 0.05) 11.4% and the apparent metabolic rate of crude protein, calcium and phosphorus were decreased (P < 0.05) by 14.9%, 18.0% and 16.1%, respectively. Meanwhile, T-2 toxin induced severe degeneration, necrosis and desquamation of the villous epithelial cells, increased inflammatory cells. Furthermore, the results of transcriptome drew that 2536 genes showed significant differences and were partially enriched in metabolic pathways, cell growth and death, apoptosis, the metabolism by CYP450, immune response pathways. Gut microbiota play a key role as microbial and duodenum genes and metabolites affected by T-2 toxin shared multiple pathways. Remarkably, Firmicutes and Proteobacteria that related to energy metabolism and inflammatory were seriously affected (P < 0.05). In summary, combined the results of integrated analysis, T-2 toxin partially induced intestine injury, potentially through changing the gene expression and the intestinal micro-ecology or damaging the intestinal mucosal directly, thus inducing inflammatory and apoptotic.


2019 ◽  
Vol 149 (10) ◽  
pp. 1766-1775 ◽  
Author(s):  
Cassondra J Saande ◽  
Joseph L Webb ◽  
Paige E Curry ◽  
Matthew J Rowling ◽  
Kevin L Schalinske

ABSTRACT Background We previously reported that a whole-egg–based diet attenuated weight gain in rats with type 2 diabetes (T2D) and more effectively maintained vitamin D status than an equivalent amount of supplemental cholecalciferol. Objectives The objective of this study was to determine the lowest dose of whole egg effective at maintaining vitamin D homeostasis and attenuating the obese phenotype in T2D rats. Methods Zucker diabetic fatty (ZDF) rats (n = 40; age 6 wk; prediabetic) and their lean controls (n = 40; age 6 wk) were randomly assigned to a diet containing 20% casein (CAS) or 20%, 10%, 5%, or 2.5% protein from whole egg (20% EGG, 10% EGG, 5% EGG, and 2.5% EGG, respectively). All diets contained 20% total protein (wt:wt). All rats received their respective diets for 8 wk, at a stage of growth and development that translates to adolescence in humans, until 14 wk of age, a point at which ZDF rats exhibit overt T2D. Weight gain was measured 5 d/wk, and circulating 25-hydroxyvitamin D [25(OH)D] was measured by ELISA. Mean values were compared by 2-factor ANOVA. Results The 20% EGG diet maintained serum 25(OH)D at 30 nmol/L in ZDF rats, whereas the 10%, 5%, and 2.5% EGG diets did not prevent insufficiency, resulting in mean serum 25(OH)D concentrations of 24 nmol/L in ZDF rats. Body weight gain was reduced by 29% (P < 0.001) and 31% (P < 0.001) in ZDF rats consuming 20% and 10% EGG diets, respectively, and by 16% (P = 0.004) and 12% (P = 0.030) in ZDF rats consuming 5% and 2.5% EGG diets, respectively, compared with CAS. Conclusions Whole-egg–based diets exerted a dose-dependent response with respect to attenuating weight gain. These data could support dietary recommendations aimed at body weight management in individuals predisposed to obesity and T2D.


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