scholarly journals Acute changes in systemic glycaemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis

2020 ◽  
Author(s):  
Wineke Bakker ◽  
Casper Gravesen Salinas ◽  
Monica Imbernon ◽  
Daniela Herrera Moro Chao ◽  
Rim Hassouna ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Area Postrema ◽  
Human Subjects ◽  
Body Weight Loss ◽  
Brain Regions ◽  
Circumventricular Organs ◽  
The Brain

ABSTRACTThe control of body weight and glucose homeostasis are the bedrock of type 2 diabetes medication. Therapies based on co-administration of glucagon-like peptide-1 (GLP-1) long-acting analogues and insulin are becoming popular in the treatment of T2D. Both insulin and GLP-1 receptors (InsR and GLP1-R, respectively) are expressed in brain regions critically involved in the regulation of energy homeostasis, suggesting a possible cooperative action. However, the mechanisms underlying the synergistic action of insulin and GLP-1R agonists on body weight loss and glucose homeostasis remain largely under-investigated. In this study, we provide evidence that peripheral insulin administration modulates the action of GLP-1R agonists onto fatty acids oxidation. Taking advantage of fluorescently labeled insulin and GLP-1R agonists, we found that glucoprivic condition, either achieved by insulin or by 2-deoxyglucose (2-DG), acts as a permissive signal on the blood-brain barrier (BBB) at circumventricular organs, including the median eminence (ME) and the area postrema (AP), enhancing the passage and action of GLP-1-R agonists. Mechanistically, this phenomenon relied on the release of tanycyctic vascular endothelial growth factor A (VEGF-A) and it was selectively impaired after calorie-rich diet exposure. Finally, we found that in human subjects, low blood glucose also correlates with enhanced blood-to-brain passage of insulin suggesting that changes in glycaemia also affect passage of peptide hormones into the brain in humans.In conclusion, we describe a yet unappreciated mechanism by which acute variations of glycaemia gate the entry and action of circulating energy-related signals in the brain. This phenomenon has physiological and clinical relevance implying that glycemic control is critical to harnessing the full benefit of GLP-1R agonist co-treatment in body weight loss therapy.

scholarly journals The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251700
Author(s):  
John W. Apolzan ◽  
Owen T. Carmichael ◽  
Krystal M. Kirby ◽  
Sreekrishna R. Ramakrishnapillai ◽  
Robbie A. Beyl ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Homeostasis ◽  
Pilot Trial ◽  
Brain Regions ◽  
Reward Processing ◽  
Daily Consumption ◽  
Fed State ◽  
Randomized Controlled ◽  
The Right ◽  
The Brain

Objective To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain. Methods In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed. Differences in fMRI signals between views of low-fat (LF (<30%)) high sugar (HS (>30%)) food, and non-food images were calculated in brain regions implicated in energy homeostasis, taste, and reward. Results All participants in the SSB (6F 4M; 8 Caucasian; 36±14 y, 28.2±5.5 kg/m2; Mean±SD) and SSS (3F 7M; 6 Caucasian; 39±12; 26.3±4.4) groups completed the study. Weight change was 0.27±0.78 kg between SSB and SSS participants. Changes in the fMRI response to LF/HS foods in reward, homeostatic and taste regions tended to not be different between the groups over the four weeks. However, activation of the right substantia nigra increased following the SSB but decreased activation following the SSS in response to LF/HS foods over 28 days (-0.32±0.12). Ratings of wanting for LF/HS foods were correlated with activation in several brain regions, including the OFC. Conclusions Change in weight was modest between the groups in this study. Daily consumption of a SSB over 28 days led to mixed responses to LF/HS foods in areas of the brain associated with reward. Ratings of wanting are correlated with fMRI activation inside an MRI scanner.

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 Therapeutic Effects of Licorice and Dried Ginger Decoction on Activity-Based Anorexia in BALB/c AnNCrl Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Do-Hyun Kim ◽  
Joong Sun Kim ◽  
Jeongsang Kim ◽  
Jong-Kil Jeong ◽  
Hong-Seok Son ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Body Weight Loss ◽  
Drop Out ◽  
Therapeutic Effects ◽  
Excessive Sweating ◽  
Dopamine Concentration ◽  
Wheel Activity ◽  
The Brain

Licorice and dried ginger decoction (Gancao-ganjiang-tang, LGD) is used for nausea and anorexia, accompanied by excessive sweating in Traditional Chinese Medicine. Herein, we investigated the therapeutic effects of LGD using the activity-based anorexia (ABA) in a mouse model. Six-week-old female BALB/c AnNCrl mice were orally administered LGD, water, licorice decoction, dried ginger decoction, or chronic olanzapine, and their survival, body weight, food intake, and wheel activity were compared in ABA. Additionally, dopamine concentration in brain tissues was evaluated. LGD significantly reduced the number of ABA mice reaching the drop-out criterion of fatal body weight loss. However, LGD showed no significant effects on food intake and wheel activity. We found that in the LGD group the rise of the light phase activity rate inhibited body weight loss. Licorice or dried ginger alone did not improve survival rates, they only showed longer survival periods than chronic olanzapine when combined. In addition, LGD increased the dopamine concentration in the brain. The results from the present study showed that LGD improves the survival of ABA mice and its mechanism of action might be related to the alteration of dopamine concentration in the brain.

scholarly journals Ghrelin and Functional Dyspepsia

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Takashi Akamizu ◽  
Hiroshi Iwakura ◽  
Hiroyuki Ariyasu ◽  
Kenji Kangawa
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Functional Dyspepsia ◽  
Body Weight Loss ◽  
New Approach ◽  
Neural Connections ◽  
Gut Function ◽  
Pathophysiological Role ◽  
Endocrine Signaling ◽  
The Brain

The majority of patients with dyspepsia have no identifiable cause of their disease, leading to a diagnosis of functional dyspepsia (FD). While a number of different factors affect gut activity, components of the nervous and endocrine systems are essential for normal gut function. Communication between the brain and gut occurs via direct neural connections or endocrine signaling events. Ghrelin, a peptide produced by the stomach, affects gastric motility/emptying and secretion, suggesting it may play a pathophysiological role in FD. It is also possible that the functional abnormalities in FD may affect ghrelin production in the stomach. Plasma ghrelin levels are reported to be altered in FD, correlating with FD symptom score. Furthermore, some patients with FD suffer from anorexia with body-weight loss. As ghrelin increases gastric emptying and promotes feeding, ghrelin therapy may be a new approach to the treatment of FD.

scholarly journals Effects of nicotine on homeostatic and hedonic components of food intake

2017 ◽  
Vol 235 (1) ◽  
pp. R13-R31 ◽  
Author(s):  
Andrea Stojakovic ◽  
Enma P Espinosa ◽  
Osman T Farhad ◽  
Kabirullah Lutfy
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
General Population ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Energy Homeostasis ◽  
Brain Areas ◽  
Nicotinic Acetylcholine ◽  
The Brain

Chronic tobacco use leads to nicotine addiction that is characterized by exaggerated urges to use the drug despite the accompanying negative health and socioeconomic burdens. Interestingly, nicotine users are found to be leaner than the general population. Review of the existing literature revealed that nicotine affects energy homeostasis and food consumption via altering the activity of neurons containing orexigenic and anorexigenic peptides in the brain. Hypothalamus is one of the critical brain areas that regulates energy balance via the action of these neuropeptides. The equilibrium between these two groups of peptides can be shifted by nicotine leading to decreased food intake and weight loss. The aim of this article is to review the existing literature on the effect of nicotine on food intake and energy homeostasis and report on the changes that nicotine brings about in the level of these peptides and their receptors that may explain changes in food intake and body weight induced by nicotine. Furthermore, we review the effect of nicotine on the hedonic aspect of food intake. Finally, we discuss the involvement of different subtypes of nicotinic acetylcholine receptors in the regulatory action of nicotine on food intake and energy homeostasis.

scholarly journals MON-637 DREADD-Induced POMCARCNeuron Activation Increases Fasting Plasma Glucose Levels Through Changes in Hepatic Gluconeogenic Gene Expression but Not Changes in the HPA Axis Activity

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luane da Guia Vieira ◽  
Alan Carlos Fernandes ◽  
Tais Nascimento ◽  
Suzelei de Castro França ◽  
Jose Antunes-Rodrigues ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Hpa Axis ◽  
Plasma Glucose ◽  
Energy Homeostasis ◽  
Body Weight Loss ◽  
Reduced Body ◽  
Hpa Axis Activity

Abstract POMC neurons expressed in the ARC are essential for energy balance and glucose homeostasis. It has been suggested the involvement of these neurons in the control of endocrine axes, such as the HPA. During fasting, POMCARC neurons are silenced as an effort to reduce body weight loss and to avoid hypoglycemia. During this process glucocorticoid secretion and activation of enzymes involved in the hepatic gluconeogenesis take place in order to preserve the homeostasis. In this study, to clarify the contribution of POMCARC neurons to the adaptive changes in energy homeostasis, glucose metabolism and HPA axis activity induced by food deprivation we used DREADDs to specifically activate POMCARC. Bilateral injections of the AAV carrying the excitatory DREADD (hM3DGq) or only the reporter gene (mCherry) have been performed into the ARC of Pomc-ires-cre and WT mice. Two weeks later the animals were fasted for 36hr, treated with saline (5 i.p. injections each 8hrs) and blood samples were collected from the facial vein at 10am. Two weeks apart, the same animals were submitted to another period of fasting and treated with CNO (1mg/Kg, 5 i.p. injections each 8hrs). Four hours after the last injection of CNO, the mice were anesthetized, blood and the liver were collected and then the animals perfused for brain harvesting. Body weight measurements have been performed before and after the 36hrs period of fasting. Another set of Pomc-ires-cre (hM3DGq or mCherry) and WT animals were fasted (36hrs), treated with CNO (5X) and subjected to GTT. DREADD–induced activation of POMCARC neurons has been confirmed by the increased cFos/mCherry expression after CNO treatment only in Pomc-ires-cre animals expressing hM3DGq. We observed that the specific activation of POMCARC neurons did not change the fasting-induced activation of HPA axis. Surprisingly, we observed reduced body weight loss and higher plasma glucose in Pomc-ires-cre animals expressing the hM3DGq and treated with CNO. The GTT showed an impaired glucose tolerance after activation of POMCARC neurons. The increased fasting glucose plasma levels was associated with increased G6pc (Glucose-6-phosphatase) mRNA expression but with no effect on other hepatic gluconeogenic genes. The present study reveals that POMCARC neurons are not involved in the increased HPA axis activity in prolonged fasting conditions. Considering the classical anorexigenic/thermogenic and the glucose-lowering action of POMCARC neurons, the present data reveal an unpredicted reduced body weight loss and impaired glucose tolerance induced by activation of these neurons during fasting. These data reinforce the notion that POMCARC neurons are heterogeneous and might be playing dual effects on energy homeostasis. Of note, because part of ARC neurons shares a common progenitor, some of the functions ascribed to POMC neurons could be mediated by non-POMC neurons expressing the Cre transgene.

scholarly journals Effects of chronic weight perturbation on energy homeostasis and brain structure in mice

2011 ◽  
Vol 300 (6) ◽  
pp. R1352-R1362 ◽  
Author(s):  
Y. Ravussin ◽  
R. Gutman ◽  
S. Diano ◽  
M. Shanabrough ◽  
E. Borok ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Energy Expenditure ◽  
Body Mass ◽  
Defense Mechanisms ◽  
Energy Homeostasis ◽  
Human Subjects ◽  
Cellular Mechanisms ◽  
Critical Question ◽  
Reduced Body

Maintenance of reduced body weight in lean and obese human subjects results in the persistent decrease in energy expenditure below what can be accounted for by changes in body mass and composition. Genetic and developmental factors may determine a central nervous system (CNS)-mediated minimum threshold of somatic energy stores below which behavioral and metabolic compensations for weight loss are invoked. A critical question is whether this threshold can be altered by environmental influences and by what mechanisms such alterations might be achieved. We examined the bioenergetic, behavioral, and CNS structural responses to weight reduction of diet-induced obese (DIO) and never-obese (CON) C57BL/6J male mice. We found that weight-reduced (WR) DIO-WR and CON-WR animals showed reductions in energy expenditure, adjusted for body mass and composition, comparable (−10–15%) to those seen in human subjects. The proportion of excitatory synapses on arcuate nucleus proopiomelanocortin neurons was decreased by ∼50% in both DIO-WR and CON-WR mice. These data suggest that prolonged maintenance of an elevated body weight (fat) alters energy homeostatic systems to defend a higher level of body fat. The synaptic changes could provide a neural substrate for the disproportionate decline in energy expenditure in weight-reduced individuals. This response to chronic weight elevation may also occur in humans. The mouse model described here could help to identify the molecular/cellular mechanisms underlying both the defense mechanisms against sustained weight loss and the upward resetting of those mechanisms following sustained weight gain.

Olanzapine Administration Reduces Chemotherapy-Induced Nausea Behavior in Rats

2021 ◽  
pp. 109980042110004
Author(s):  
Rosario B. Jaime-Lara ◽  
Tito Borner ◽  
Ruby A. Holland ◽  
Evan Shaulson ◽  
Brianna Brooks ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Side Effects ◽  
Energy Balance ◽  
Food Intake ◽  
Body Weight Loss ◽  
Brain Regions ◽  
Nausea And Vomiting ◽  
Behavioral Experiments ◽  
Mrna Expression Levels

Nausea and vomiting are consistently identified among the most distressing side effects of chemotherapy. In recent years, Olanzapine (OLZ) treatment was added to anti-emetic guidelines as a treatment for chemotherapy-induced nausea and vomiting (CINV), despite little available data supporting a mechanism behind the positive benefits of the drug. Here, we examine whether OLZ reduces cisplatin chemotherapy-induced side effects on food intake and pica behavior in rats (i.e., kaolin intake, a proxy for nausea/emesis). Behavioral experiments tested whether systemic or hindbrain administration of OLZ ameliorated cisplatin-induced pica, anorexia, and body weight loss in rats. We also tested whether systemic OLZ reduces cisplatin-induced neuronal activation in the dorsal vagal complex (DVC), a hindbrain region controlling emesis. Lastly, given their role in regulating feeding and emesis, circulating ghrelin levels and central mRNA expression levels of serotonin (HT) receptor subunits, including 5-HT2C, were measured in brain regions that regulate CINV and energy balance in an exploratory analysis to investigate potential mediators of OLZ action. Our results show that both systemic and hindbrain administration of OLZ attenuated cisplatin-induced kaolin intake and body weight loss, but not anorexia. Systemic OLZ decreased cisplatin-induced c-Fos immunofluorescence in the DVC and prevented cisplatin-induced reductions in circulating ghrelin levels. IP OLZ also blocked cisplatin-induced increases in Htr2c expression in DVC and hypothalamic micropunches. These data suggest hindbrain exposure to OLZ is sufficient to induce reductions in cisplatin-induced pica and that central serotonergic signaling, via 5-HT2C, and changes in circulating ghrelin may be potential mediators of olanzapine anti-emetic action.

scholarly journals Sensory Circumventricular Organs, Neuroendocrine Control, and Metabolic Regulation

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 494
Author(s):  
Jin Kwon Jeong ◽  
Samantha A. Dow ◽  
Colin N. Young
Keyword(s):  
Blood Brain Barrier ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Area Postrema ◽  
Brain Regions ◽  
Circumventricular Organs ◽  
Brain Barrier ◽  
Neuroendocrine Control ◽  
Blood Brain ◽  
Cellular Machinery

The central nervous system is critical in metabolic regulation, and accumulating evidence points to a distributed network of brain regions involved in energy homeostasis. This is accomplished, in part, by integrating peripheral and central metabolic information and subsequently modulating neuroendocrine outputs through the paraventricular and supraoptic nucleus of the hypothalamus. However, these hypothalamic nuclei are generally protected by a blood-brain-barrier limiting their ability to directly sense circulating metabolic signals—pointing to possible involvement of upstream brain nuclei. In this regard, sensory circumventricular organs (CVOs), brain sites traditionally recognized in thirst/fluid and cardiovascular regulation, are emerging as potential sites through which circulating metabolic substances influence neuroendocrine control. The sensory CVOs, including the subfornical organ, organum vasculosum of the lamina terminalis, and area postrema, are located outside the blood-brain-barrier, possess cellular machinery to sense the metabolic interior milieu, and establish complex neural networks to hypothalamic neuroendocrine nuclei. Here, evidence for a potential role of sensory CVO-hypothalamic neuroendocrine networks in energy homeostasis is presented.

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