Effects of olanzapine on muscarinic M3 receptor binding density in the brain relates to weight gain, plasma insulin and metabolic hormone levels

2012 ◽  
Vol 22 (5) ◽  
pp. 364-373 ◽  
Author(s):  
Katrina Weston-Green ◽  
Xu-Feng Huang ◽  
Jiamei Lian ◽  
Chao Deng
1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.


1993 ◽  
Vol 14 (8) ◽  
pp. 634-643 ◽  
Author(s):  
N. P.L.G. VERHOEFF ◽  
B. ERBAS ◽  
O. KAPUCU ◽  
E. BUSEMANN SOKOLE ◽  
H. BLOK ◽  
...  

2016 ◽  
Vol 48 (7) ◽  
pp. 491-501 ◽  
Author(s):  
Madeliene Stump ◽  
Deng-Fu Guo ◽  
Ko-Ting Lu ◽  
Masashi Mukohda ◽  
Xuebo Liu ◽  
...  

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.


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.


2000 ◽  
Vol 70 (2) ◽  
pp. 349-362 ◽  
Author(s):  
A.F. Carson ◽  
A.R.G. Wylie ◽  
J.D.G. McEvoy ◽  
M. McCoy ◽  
L.E.R. Dawson

AbstractSeventy high genetic merit Holstein heifers were used in two experiments to investigate (1) the effects of plane of nutrition and diet type during the pre-pubertal period and (2) the effects of plane of nutrition during the post-pubertal period on metabolic hormone concentrations, growth and milk production. In experiment 1, treatment 1 and 2 heifers were given food to achieve a live-weight gain of 0·70 and 0·95 kg/day from 3 to 10 months of age on a grass silage based diet, while treatment 3 heifers were given food to achieve 0·95 kg/day on a barley straw/concentrate diet. During the pre-pubertal period, heifers reared on treatment 1 had significantly higher growth hormone(GH) concentrations (ng/ml per 1 h) than heifers reared on treatment 2 (P < 0·01) and had significantly lower insulin concentrations than heifers reared on treatment 3 (P < 0·01). Heifers reared on treatment 1 had significantly lower insulin-like growth factor 1 (IGF-1) concentrations than those reared on treatment 3 (P < 0·01). At 10 months of age heifers reared on treatment 1 were of lower condition score (P < 0·01) than those on treatment 2 and had a smaller heart girth diameter (P < 0·01) than those on treatments 2 and 3. During the first lactation, milk yield and composition produced by the heifers was not significantly affected by treatment. In experiment 2, treatment A heifers were given, from 14 to 24 months of age, a low plane of nutrition to allow a live-weight gain of 0·65 kg/day on a grass silage and grass based diet during the winter and summer periods respectively. Treatment B heifers were kept on a high plane of nutrition to allow a live-weight gain of 0·90 kg/day on the same forage along with concentrate supplementation. During the rearing period, GH and IGF-1 concentrations were not significantly affected by treatment. Treatment A heifers weighed less before calving (P < 0·05), had a lower condition score (P < 0·01), and had a smaller heart girth diameter (P < 0·01) than those on treatment B. During the first 10 weeks of lactation, heifers on treatment A had a higher silage dry matter intake and lost less weight (P < 0·05) than those on treatment B, however, by 20 weeks of lactation these effects had disappeared. Milk yield and composition during the first lactation were not significantly affected by treatment. Overall, the findings of experiments 1 and 2 did not show any beneficial effects of higher weights at first calving in high genetic merit Holsteins and therefore indicate that accelerated growth in the pre- or post-pubertal period may not be required.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.


2020 ◽  
Author(s):  
Clayton Spada ◽  
Chau Vu ◽  
Iona Raymond ◽  
Warren Tong ◽  
Chia-Lin Chuang ◽  
...  

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.


2016 ◽  
Vol 68 (6) ◽  
pp. 1487-1496 ◽  
Author(s):  
D.S. Lucas ◽  
E.T.F. Siqueira ◽  
M.M.H. Haguiwara ◽  
S.S. Azevedo ◽  
S.E. Yotsuyanagi ◽  
...  

ABSTRACT A non-surgical sterilant (NSS) was used with the objective of assessing the zootechnical performance, carcass and meat quality, and hormone levels. 90 male piglets were selected with birthweights varying between 1.5kg to 2.0kg. The control group was constituted of 45 males castrated by the conventional surgical method, at the seventh day of age, and the treated group was constituted of 45 males castrated with NSS (active principle of zinc gluconate in the concentration of 26.2mg/mL associated to the dimethyl sulfoxide at 0.5%), with the application of the first dose on the seventh day of age and the second dose on the fourteenth day of age. The zootechnical assessments were carried out on the farm and consisted: weight gain in the periods per animal and feed conversion. The slaughter of the animals and the assessment of the carcass and meat quality and hormone levels were carried out in a slaughterhouse and the municipality of Campinas (SP). The study demonstrated that the use of NSS was a viable alternative in relation to the zootechnical performance and the carcass quality. In relation to the meat quality there was no significant difference in the majority of the assessed parameters.


2000 ◽  
Vol 278 (6) ◽  
pp. E1097-E1103 ◽  
Author(s):  
Carmen Alvarez ◽  
Danielle Bailbe ◽  
Françoise Picarel-Blanchot ◽  
Eric Bertin ◽  
Ana-Maria Pascual-Leone ◽  
...  

The availability of the Goto-Kakisaki (GK) rat model of non-insulin-dependent diabetes mellitus prompted us to test the effect of a limited period of undernutrition in previously diabetic young rats on their insulin secretion and insulin action during adult age. Four-week-old female GK rats were either food restricted (35% restriction, 15% protein diet) or protein and energy restricted (35% restriction, 5% protein diet) for 4 wk. Food restriction in the young GK rat lowered weight gain but did not aggravate basal hyperglycemia or glucose intolerance, despite a decrease in basal plasma insulin level. Furthermore, the insulin-mediated glucose uptake by peripheral tissues in the GK rat was clearly improved. We also found that food restriction, when it is coupled to overt protein deficiency in the young GK rat, altered weight gain more severely and slightly decreased basal hyperglycemia but conversely aggravated glucose tolerance. Improvement of basal hyperglycemia was related to repression of basal hepatic glucose hyperproduction, despite profound attenuation of basal plasma insulin level. Deterioration of tolerance to glucose was related to severe blunting of the residual glucose-induced insulin secretion. It is, however, likely that the important enhancement of the insulin-mediated glucose uptake helped to limit the deterioration of glucose tolerance.


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