CB1Rs in VMH Neurons Regulate Glucose Homeostasis but not Body Weight

2021 ◽  
Author(s):  
Carlos M Castorena ◽  
Alexandre Caron ◽  
Natalie J Michael ◽  
Newaz I Ahmed ◽  
Amanda G Arnold ◽  
...  
Keyword(s):  
Body Weight ◽  
Side Effects ◽  
Glucose Homeostasis ◽  
Ventromedial Hypothalamus ◽  
Metabolic Effects ◽  
Peripheral Tissues ◽  
Inverse Agonists ◽  
Affect Body Weight ◽  
The Central Nervous System ◽  
Key Sites

Cannabinoid 1 receptor (CB1R) inverse-agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse-agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that deletion of CB1Rs in the VMH did not affect body weight in male and female mice fed chow or HFD. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse-agonists SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice.

Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model

2021 ◽  
Author(s):  
Camille Marciniak ◽  
Oscar Chávez-Talavera ◽  
Robert Caiazzo ◽  
Thomas Hubert ◽  
Lorea Zubiaga ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Body Weight ◽  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Body Weight Loss ◽  
Metabolic Effects ◽  
One Anastomosis Gastric Bypass ◽  
Alimentary Limb ◽  
The Common

Background/Objectives: The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the One Anastomosis Gastric Bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces stronger beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the biliary and common limbs in the weight-loss and metabolic effects that occur upon OAGB. Subjects/Methods: OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen-like minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. Results: OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Conclusions: Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss.

scholarly journals Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

2013 ◽  
Vol 16 (7) ◽  
pp. 1661-1666 ◽  
Author(s):  
Viacheslav Terevnikov ◽  
Jan-Henry Stenberg ◽  
Jari Tiihonen ◽  
Evgeni Chukhin ◽  
Marina Joffe ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Side Effects ◽  
First Generation ◽  
Metabolic Effects ◽  
Open Label ◽  
Double Blind ◽  
Cholesterol Levels ◽  
Syndrome Scale ◽  
Negative Syndrome

Abstract Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination – a novel observation with possible clinical and theoretical implications.

scholarly journals Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity

Endocrinology ◽  
2013 ◽  
Vol 154 (7) ◽  
pp. 2481-2488 ◽  
Author(s):  
Caroline Fernandes-Santos ◽  
Zhongming Zhang ◽  
Donald A. Morgan ◽  
Deng-Fu Guo ◽  
Andrew F. Russo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
The Central Nervous System

Abstract The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.

scholarly journals Gsα Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 600-610 ◽  
Author(s):  
Alta Berger ◽  
Ahmed Kablan ◽  
Catherine Yao ◽  
Thuy Ho ◽  
Brandon Podyma ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Ventromedial Hypothalamus ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Paternal Allele ◽  
Molecular Evidence ◽  
High Fat ◽  
Leptin Sensitivity ◽  
Parent Of Origin

Abstract In both mice and patients with Albright hereditary osteodystrophy, heterozygous inactivating mutations of Gsα, a ubiquitously expressed G protein that mediates receptor-stimulated intracellular cAMP production, lead to obesity and insulin resistance but only when the mutation is present on the maternal allele. This parent-of-origin effect in mice was shown to be due to Gsα imprinting in one or more brain regions. The ventromedial hypothalamus (VMH) is involved in the regulation of energy and glucose homeostasis, but the role of Gsα in VMH on metabolic regulation is unknown. To examine this, we created VMH-specific Gsα-deficient mice by mating Gsα-floxed mice with SF1-cre mice. Heterozygotes with Gsα mutation on either the maternal or paternal allele had a normal metabolic phenotype, and there was no molecular evidence of Gsα imprinting, indicating that the parent-of-origin metabolic effects associated with Gsα mutations is not due to Gsα deficiency in VMH SF1 neurons. Homozygous VMH Gsα knockout mice (VMHGsKO) showed no changes in body weight on either a regular or high-fat diet. However, glucose metabolism (fasting glucose, glucose tolerance, insulin sensitivity) was significantly improved in male VMHGsKO mice, with the difference more dramatic on the high-fat diet. In addition, male VMHGsKO mice on the high-fat diet showed a greater anorexigenic effect and increased VMH signal transducer and activator of transcription-3 phosphorylation in response to leptin. These results indicate that VMH Gsα/cyclic AMP signaling regulates glucose homeostasis and alters leptin sensitivity in mice, particularly in the setting of excess caloric intake.

Circadian rhythm, sleep pattern, and metabolic consequences: an overview on cardiovascular risk factors

2014 ◽  
Vol 18 (1) ◽  
Author(s):  
Roberta Marcondes Machado ◽  
Marcia Kiyomi Koike
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Circadian Rhythm ◽  
Sleep Pattern ◽  
Metabolic Effects ◽  
Environmental Cues ◽  
Suprachiasmatic Nuclei ◽  
Peripheral Tissues ◽  
The Central Nervous System ◽  
Central Clock

AbstractSleep duration is a risk factor for cardiovascular disease. Alteration in sleep pattern can induce the loss of circadian rhythmicity. Chronically, this desynchronization between endogenous rhythm and behavioral cycles can lead to an adverse metabolic profile, a proinflammatory condition and can increase the risk of cardiovascular disease. The circadian cycle can vary due to environmental cues. The circadian pacemaker is located in the suprachiasmatic nuclei; this central clock coordinates the circadian rhythm in the central nervous system and peripheral tissues. The mechanisms involved in sleep disturbance, circadian misalignment and adverse metabolic effects have yet to be fully elucidated. This review looks over the association among sleep alteration, circadian rhythm and the development of risk factors implicated in cardiovascular disease.

scholarly journals MON-028 Chronic Resveratrol Exposure Improves Glucose Homeostasis and Cardiac Function in a Rat Model of Polycystic Ovarian Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rogelio Enrique Molina ◽  
Tiffany Shao ◽  
Harmanprit Randhawa ◽  
Vanessa Hoang ◽  
Arpita Kalla Vyas
Keyword(s):  
Body Weight ◽  
Glucose Homeostasis ◽  
Rat Model ◽  
Rodent Model ◽  
Female Rats ◽  
Metabolic Effects ◽  
Metabolic Phenotype ◽  
Glucose Excursion ◽  
Beneficial Effects ◽  
Significant Difference

Abstract Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age, with a prevalence of 5-8%. Long-term complications seen in PCOS include cardiovascular disease and type 2 Diabetes Mellitus. Current therapies do not completely address the cardiometabolic perturbations seen in women with PCOS. Resveratrol (RSV), a natural polyphenol, is shown to have beneficial cardio-metabolic effects in various pathological conditions including that on insulin sensitivity, cardiovascular function. In-vitro studies suggest it’s beneficial effects on ovarian function as well. Therefore, we hypothesized that chronic exposure to RSV would improve both cardiovascular and metabolic phenotypes in PCOS. To test this hypothesis we used an established rat model of PCOS that develops metabolic derangement and irregular cycles. A 7.5 mg (90-day release) dihydrotestosterone (DHT) pellet providing a daily dose of 83 mcg was implanted in 5-week-old female rats. Studies were also conducted on littermate matched controls (C) with no DHT implant. A subgroup of the control and DHT treated rats (n=6 per group) received a 0.84 g/kg dose of resveratrol (RSV) in their chow starting at age 5 weeks. At 8 weeks, animals were weighed weekly (n=6 per group). Oral glucose tolerance test (OGTT n=6 per group) and cardiac echocardiogram (C n=12, C+RSV n=6, DHT n=10, DHT+RSV n=6) were conducted at 16-weeks of age. Body weight increased significantly in DHT treated rats compared to C between 8 and 16 weeks (40 vs 22 grams, p <0.001). RSV treatment did not mitigate the effects of DHT on body weight (34 vs 40 grams, p>0.5). There was significantly higher glucose excursion at 30 minutes post glucose load in both DHT (148± 7.4 mg/dl) and DHT+RSV (139± 7.4 mg/dl) compared to C group (121± 13 mg/dl, p<0.001, p=0.03 respectively). However, by 60 and 90 minutes only DHT group had a significantly higher glucose excursion compared to both DHT+RSV and C groups (131± 4.1,124± 5.7,110 ± 5.9 mg/dl, p=0.015,p=0.21 respectively); 90min (118±5.8,110±4.7,96±4.2 mg/dl, p<0.01,p=0.09 respectively). By 120 minutes, no significant difference in glucose levels existed between groups. Cardiac echocardiogram showed significantly lower mitral valve E/A ratio (and increased MV isovolumic relaxation time (IVRT) in DHT group compared to C. RSV treatment reversed these changes. In conclusion, RSV improved glucose homeostasis and diastolic dysfunction in the DHT induced rodent model of PCOS and may serve as a novel treatment option targeting the cardiometabolic derangement seen in PCOS. Further studies elucidating the mechanisms underlying the beneficial effects of RSV on cardio-metabolic phenotype in this PCOS rodent model is warranted.

scholarly journals The Impact of Artificial Sweeteners on Body Weight Control and Glucose Homeostasis

2021 ◽  
Vol 7 ◽  
Author(s):  
Michelle D. Pang ◽  
Gijs H. Goossens ◽  
Ellen E. Blaak
Keyword(s):  
Body Weight ◽  
Glucose Homeostasis ◽  
Weight Control ◽  
Overweight And Obesity ◽  
Metabolic Effects ◽  
Artificial Sweeteners ◽  
Artificial Sweetener ◽  
Body Weight Control ◽  
The Impact

A poor diet is one of the leading causes for non-communicable diseases. Due to the increasing prevalence of overweight and obesity, there is a strong focus on dietary overconsumption and energy restriction. Many strategies focus on improving energy balance to achieve successful weight loss. One of the strategies to lower energy intake is refraining from sugars and replacing them with artificial sweeteners, which maintain the palatability without ingesting calories. Nevertheless, the safety and health benefits of artificial sweeteners consumption remain a topic of debate within the scientific community and society at large. Notably, artificial sweeteners are metabolized differently from each other due to their different properties. Therefore, the difference in metabolic fate of artificial sweeteners may underlie conflicting findings that have been reported related to their effects on body weight control, glucose homeostasis, and underlying biological mechanisms. Thus, extrapolation of the metabolic effects of a single artificial sweetener to all artificial sweeteners is not appropriate. Although many rodent studies have assessed the metabolic effects of artificial sweeteners, long-term studies in humans are scarce. The majority of clinical studies performed thus far report no significant effects or beneficial effects of artificial sweeteners on body weight and glycemic control, but it should be emphasized that the study duration of most studies was limited. Clearly, further well-controlled, long-term human studies investigating the effects of different artificial sweeteners and their impact on gut microbiota, body weight regulation and glucose homeostasis, as well as the underlying mechanisms, are warranted.

scholarly journals NEURONAL FGF-21 SIGNALING: A SENSOR OF DIETARY PROTEIN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Cristal Hill ◽  
Christopher Morrison
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
Dietary Protein ◽  
Protein Restriction ◽  
Fibroblast Growth Factor 21 ◽  
Dietary Protein Restriction ◽  
Reduced Body ◽  
Low Protein ◽  
The Central Nervous System

Abstract Our data demonstrates that dietary protein restriction increases energy expenditure and improves glucose homeostasis, and that this effect is largely mediated by the metabolic hormone fibroblast growth factor 21(FGF21). Considering that the central nervous system (CNS) is acknowledged as a major regulator of both energy and glucose homeostasis, we have extended our studies to identify the tissue site mediating these FGF21-dependent effects via dietary protein restriction. In this study, mice with dysfunctional FGF21-signaling in either the CNS or adipose tissue were fed a control or low protein (LP)-diet to assess changes in body weight and metabolic endpoints. Our data show that LP diet increased energy expenditure and reduced body weight in control littermates, but these effects were lost in mice bearing CNS-specific deletion of Klb. These data highlight a liver to brain FGF21-signal as the first known neuroendocrine mechanism to explain the coordinated metabolic changes induced by dietary protein restriction.

scholarly journals Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy

2016 ◽  
Vol 34 (35) ◽  
pp. 4261-4269 ◽  
Author(s):  
Gadi Shlomai ◽  
Brian Neel ◽  
Derek LeRoith ◽  
Emily Jane Gallagher
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Homeostasis ◽  
Cancer Incidence ◽  
Metabolic Effects ◽  
Peripheral Tissues ◽  
Cancer Data ◽  
Incidence And Mortality

Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis. Results T2DM is associated with an increased risk and greater mortality from many cancer types. Metformin use has been associated with a decrease in cancer incidence and mortality, and there are many ongoing randomized trials investigating the effects of metformin on cancer-related outcomes. However, data regarding the association of other antidiabetes medications with cancer incidence and mortality are conflicting. Glucocorticoids, hormone-based therapies, inhibitors that target the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway, and insulin-like growth factor 1 receptor–targeted therapy have been associated with high rates of hyperglycemia. These agents mediate their deleterious metabolic effects by reducing insulin secretion and increasing insulin resistance in peripheral tissues. Conclusion Studies must be performed to optimize cancer screening strategies in individuals with T2DM. A greater understanding of the mechanisms that link diabetes and cancer are needed to identify targets for therapy in individuals with diabetes who develop cancer. Data from clinical studies are needed to further elucidate the effects of antidiabetic medications on cancer incidence and progression. As several anticancer therapies alter glucose homeostasis, physicians need to be aware of these potential effects. Careful patient screening and monitoring during treatment with these agents is necessary.

Dopaminergic therapy does not affect body weight in Parkinson's disease patients

2006 ◽  
Vol 33 (S 1) ◽  
Author(s):  
C.G. Bachmann ◽  
C. Werner ◽  
E. Brunner ◽  
C. Trenkwalder
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Body Weight ◽  
Dopaminergic Therapy ◽  
Affect Body Weight
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