| 1. |
- Vargas, J. E., et al.
(författare)
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Dietary supplemental plant oils reduce methanogenesis from anaerobic microbial fermentation in the rumen
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Ruminants contribute to the emissions of greenhouse gases, in particular methane, due to the microbial anaerobic fermentation of feed in the rumen. The rumen simulation technique was used to investigate the effects of the addition of different supplemental plant oils to a high concentrate diet on ruminal fermentation and microbial community composition. The control (CTR) diet was a high-concentrate total mixed ration with no supplemental oil. The other experimental diets were supplemented with olive (OLV), sunflower (SFL) or linseed (LNS) oils at 6%. Rumen digesta was used to inoculate the fermenters, and four fermentation units were used per treatment. Fermentation end-products, extent of feed degradation and composition of the microbial community (qPCR) in digesta were determined. Compared with the CTR diet, the addition of plant oils had no significant (P>0.05) effect on ruminal pH, substrate degradation, total volatile fatty acids or microbial protein synthesis. Gas production from the fermentation of starch or cellulose were decreased by oil supplementation. Methane production was reduced by 21-28% (P<0.001), propionate production was increased (P<0.01), and butyrate and ammonia outputs and the acetate to propionate ratio were decreased (P<0.001) with oil-supplemented diets. Addition of 6% OLV and LNS reduced (P<0.05) copy numbers of total bacteria relative to the control. In conclusion, the supplementation of ruminant diets with plant oils, in particular from sunflower or linseed, causes some favorable effects on the fermentation processes. The addition of vegetable oils to ruminant mixed rations will reduce methane production increasing the formation of propionic acid without affecting the digestion of feed in the rumen. Adding vegetable fats to ruminant diets seems to be a suitable approach to decrease methane emissions, a relevant cleaner effect that may contribute to alleviate the environmental impact of ruminant production.
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| 2. |
- Vargas, J. E., et al.
(författare)
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Effect of Sunflower and Marine Oils on Ruminal Microbiota, In vitro Fermentation and Digesta Fatty Acid Profile
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- This study using the rumen simulation technique (RUSITEC) investigated the changes in the ruminal microbiota and anaerobic fermentation in response to the addition of different lipid supplements to a ruminant diet. A basal diet with no oil added was the control, and the treatment diets were supplemented with sunflower oil (2%) only, or sunflower oil (2%) in combination with fish oil (1%) or algae oil (1%). Four fermentation units were used per treatment. RUSITEC fermenters were inoculated with rumen digesta. Substrate degradation, fermentation end-products (volatile fatty acids, lactate, gas, methane, and ammonia), and microbial protein synthesis were determined. Fatty acid profiles and microbial community composition were evaluated in digesta samples. Numbers of representative bacterial species and microbial groups were determined using qPCR. Microbial composition and diversity were based on T-RFLP spectra. The addition of oils had no effect on substrate degradation or microbial protein synthesis. Differences among diets in neutral detergent fiber degradation were not significant (P = 0.132), but the contrast comparing oil-supplemented diets with the control was significant (P = 0.039). Methane production was reduced (P < 0.05) with all oil supplements. Propionate production was increased when diets containing oil were fermented. Compared with the control, the addition of algae oil decreased the percentage C18: 3 c9c12c15 in rumen digesta, and that of C18: 2 c9t11 was increased when the control diet was supplemented with any oil. Marine oils decreased the hydrogenation of C18 unsaturated fatty acids. Microbial diversity was not affected by oil supplementation. Cluster analysis showed that diets with additional fish or algae oils formed a group separated from the sunflower oil diet. Supplementation with marine oils decreased the numbers of Butyrivibrio producers of stearic acid, and affected the numbers of protozoa, methanogens, Selenomonas ruminantium and Streptococcus bovis, but not total bacteria. In conclusion, there is a potential to manipulate the rumen fermentation and microbiota with the addition of sunflower, fish or algae oils to ruminant diets at appropriate concentrations. Specifically, supplementation of ruminant mixed rations with marine oils will reduce methane production, the acetate to propionate ratio and the fatty acid hydrogenation in the rumen.
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| 3. |
- Vargas, J. E., et al.
(författare)
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Effects of supplemental plant oils on rumen bacterial community profile and digesta fatty acid composition in a continuous culture system (RUSITEC)
- 2020
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Ingår i: Anaerobe. - : Elsevier BV. - 1075-9964 .- 1095-8274. ; 61
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Tidskriftsartikel (refereegranskat)abstract
- Lipid supplementation of ruminant diets may trigger changes in the ruminal microbiota and in anaerobic digestion. Changes in the bacterial community composition and in the fatty acid hydrogenation caused by the addition of different supplemental plant oils to a high concentrate diet were investigated in vitro using RUSITEC (rumen simulation technique) fermenters. The control (CTR) diet was a high-concentrate total mixed ration for dairy sheep, with no supplementary oil. The other experimental diets were supplemented with olive (OLV), sunflower (SFL) or linseed (LNS) oils at 6% (dry matter basis). Four RUSITEC fermenters were used for each experimental diet, all inoculated with rumen digesta of sheep. Extent of dry matter and fat degradation, composition of the bacterial community and long-chain fatty acids in digesta were determined. The addition of plant oils increased (P < 0.001) apparent degradation of fat in the fermenters, whereas fermentation kinetics (gas production and average fermentation rate) were lower (P < 0.05) with the LNS than with the CTR diet. Hydrogenation of C18 unsaturated fatty acids (P < 0.05), in particular that of oleic acid (P < 0.001), and stearic acid proportion (P < 0.001) were reduced, and oleic acid proportion was increased (P < 0.001) with all oil supplements. Addition of OLV decreased linoleic and LNS increased α-linolenic (P < 0.001), whereas conjugated linoleic was increased with SFL oil (P = 0.025) and vaccenic increased with both SFL and LNS oils (P = 0.008). Addition of 6% OLV and LNS reduced (P < 0.05) microbial community diversity and quantity of total bacteria relative to the control. Some specific microbial groups were affected (P < 0.001) by oil addition, with less relative abundance of Clostridiales and Actinobacteria and increased Bacteroidales, Aeromonadales and Lactobacillales species. In conclusion, the supplementation of high-concentrate ruminant diets with plant oils, in particular from sunflower or linseed, causes shifts in the rumen microbiota and fatty acid hydrogenation in the rumen increasing the formation of vaccenic and conjugated linoleic acids.
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| 4. |
- Anderberg, Rozita H, 1976, et al.
(författare)
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Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 1062-1073
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT2A) and 5-HT2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT2A, but surprisingly not the 5-HT2C, receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation.
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| 5. |
- Eerola, Kim, 1982, et al.
(författare)
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Hindbrain insulin controls feeding behavior
- 2022
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 66
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Pancreatic insulin was discovered a century ago, and this discovery led to the first lifesaving treatment for diabetes. While still controversial, nearly one hundred published reports suggest that insulin is also produced in the brain, with most focusing on hypothalamic or cortical insulin-producing cells. However, specific function for insulin produced within the brain remains poorly understood. Here we identify insulin expression in the hindbrain's dorsal vagal complex (DVC), and determine the role of this source of insulin in feeding and metabolism, as well as its response to diet-induced obesity in mice. Methods: To determine the contribution of Ins2-producing neurons to feeding behavior in mice, we used the cross of transgenic RipHER-cre mouse and channelrhodopsin-2 expressing animals, which allowed us to optogenetically stimulate neurons expressing Ins2 in vivo. To confirm the presence of insulin expression in Rip-labeled DVC cells, in situ hybridization was used. To ascertain the specific role of insulin in effects discovered via optogenetic stimulation a selective, CNS applied, insulin receptor antagonist was used. To understand the physiological contribution of insulin made in the hindbrain a virogenetic knockdown strategy was used. Results: Insulin gene expression and presence of insulin-promoter driven fluorescence in rat insulin promoter (Rip)-transgenic mice were detected in the hypothalamus, but also in the DVC. Insulin mRNA was present in nearly all fluorescently labeled cells in DVC. Diet-induced obesity in mice altered brain insulin gene expression, in a neuroanatomically divergent manner; while in the hypothalamus the expected obesity-induced reduction was found, in the DVC diet-induced obesity resulted in increased expression of the insulin gene. This led us to hypothesize a potentially divergent energy balance role of insulin in these two brain areas. To determine the acute impact of activating insulin-producing neurons in the DVC, optic stimulation of light-sensitive channelrhodopsin 2 in Rip-transgenic mice was utilized. Optogenetic photoactivation induced hyperphagia after acute activation of the DVC insulin neurons. This hyperphagia was blocked by central application of the insulin receptor antagonist S961, suggesting the feeding response was driven by insulin. To determine whether DVC insulin has a necessary contribution to feeding and meta-bolism, virogenetic insulin gene knockdown (KD) strategy, which allows for site-specific reduction of insulin gene expression in adult mice, was used. While chow-fed mice failed to reveal any changes of feeding or thermogenesis in response to the KD, mice challenged with a high-fat diet consumed less food. No changes in body weight were identified, possibly resulting from compensatory reduction in thermogenesis. Conclusions: Together, our data suggest an important role for hindbrain insulin and insulin-producing cells in energy homeostasis. (c) 2022 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 6. |
- López-Ferreras, Lorena, et al.
(författare)
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Ghrelin's control of food reward and body weight in the lateral hypothalamic area is sexually dimorphic
- 2017
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Ingår i: Physiology & Behavior. - : Elsevier BV. - 0031-9384. ; 176, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a stomach-produced hormone that stimulates ingestive behavior and increases motivated behavior to obtain palatable foods. Ghrelin receptors (growth hormone secretagogue receptors; Ghsr) are expressed in the lateral hypothalamic area (LHA), and LHA-targeted ghrelin application increases ingestive behavior in male rodents. However, the effects of LHA ghrelin signaling in females are unexplored. Here we investigated whether LHA ghrelin signaling is necessary and sufficient for control of ingestive and motivated behavior for food in male and female rats. Ghrelin delivered to the LHA increased food intake and motivated behavior for sucrose in both male and female rats, whereas increased food-seeking behavior and body weight were only observed in females. Females had slightly higher Ghsr levels in the LHA compared to males, and importantly, acute blockade of the Ghsr in the LHA significantly reduced food intake, body weight, and motivated behavior for sucrose in female but not male rats. Chronic LHA Ghsr reduction in female rats achieved by RNA inference-mediated Ghsr knockdown, resulting in a 25% reduction in LHA Ghsr mRNA, abolished the reward-driven behavioral effects of LHA-targeted ghrelin, but was not sufficient to affect baseline food intake or food reward responding. Collectively we show that ghrelin acts in the LHA to alter ingestive and motivated behaviors in a sex-specific manner. (C) 2017 The Authors. Published by Elsevier Inc.
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| 7. |
- López-Ferreras, Lorena, et al.
(författare)
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GLP-1 modulates the supramammillary nucleus-lateral hypothalamic neurocircuit to control ingestive and motivated behavior in a sex divergent manner
- 2019
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 20, s. 178-193
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The supramammillary nucleus (SuM) is nestled between the lateral hypothalamus (LH) and the ventral tegmental area (VTA). This neuroanatomical position is consistent with a potential role of this nucleus to regulate ingestive and motivated behavior. Here neuroanatomical, molecular, and behavior approaches are utilized to determine whether SuM contributes to ingestive and food-motivated behavior control. Methods: Through the application of anterograde and retrograde neural tract tracing with novel designer viral vectors, the current findings show that SuM neurons densely innervate the LH in a sex dimorphic fashion. Glucagon-like peptide-1 (GLP-1) is a clinically targeted neuro-intestinal hormone with a well-established role in regulating energy balance and reward behaviors. Here we determine that GLP-1 receptors (GLP-1R) are expressed throughout the SuM of both sexes, and also directly on SuM LH-projecting neurons and investigate the role of SuM GLP-1R in the regulation of ingestive and motivated behavior in male and female rats. Results: SuM microinjections of the GLP-1 analogue, exendin-4, reduced ad libitum intake of chow, fat, or sugar solution in both male and female rats, while food-motivated behaviors, measured using the sucrose motivated operant conditioning test, was only reduced in male rats. These data contrasted with the results obtained from a neighboring structure well known for its role in motivation and reward, the VTA, where females displayed a more potent response to GLP-1R activation by exendin-4. In order to determine the physiological role of SuM GLP-1R signaling regulation of energy balance, we utilized an adeno-associated viral vector to site-specifically deliver shRNA for the GLP-1R to the SuM. Surprisingly, and in contrast to previous results for the two SuM neighboring sites, LH and VTA, SuM GLP-1R knockdown increased food seeking and adiposity in obese male rats without altering food intake, body weight or food motivation in lean or obese, female or male rats. Conclusion: Taken together, these results indicate that SuM potently contributes to ingestive and motivated behavior control; an effect contingent on sex, diet/homeostatic energy balance state and behavior of interest. These data also extend the map of brain sites directly responsive to GLP-1 agonists, and highlight key differences in the role that GLP-1R play in interconnected and neighboring nuclei. (C) 2018 The Authors. Published by Elsevier GmbH.
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| 8. |
- López-Ferreras, Lorena, et al.
(författare)
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Key role for hypothalamic interleukin-6 in food-motivated behavior and body weight regulation
- 2021
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The pro-inflammatory role of interleukin-6 (IL-6) is well-characterized. Blockade of IL-6, by Tocilizumab, is used in patients with rheumatoid arthritis and those diagnosed with cytokine storm. However, brain-produced IL-6 has recently emerged as a critical mediator of gut/adipose communication with the brain. Central nervous system (CNS) IL-6 is engaged by peripheral and central signals regulating energy homeostasis. IL-6 is critical for mediating hypophagia and weight loss effects of a GLP-1 analog, exendin-4, a clinically utilized drug. However, neuroanatomical substrates and behavioral mechanisms of brain IL-6 energy balance control remain poorly understood. We propose that the lateral hypothalamus (LH) is an IL-6-harboring brain region, key to food intake and food reward control. Microinjections of IL-6 into the LH reduced chow and palatable food intake in male rats. In contrast, female rats responded with reduced motivated behavior for sucrose, measured by the progressive ratio operant conditioning test, a behavioral mechanism previously not linked to IL-6. To test whether IL-6, produced in the LH, is necessary for ingestive and motivated behaviors, and body weight homeostasis, virogenetic knockdown by infusion of AAV-siRNA-IL6 into the LH was utilized. Attenuation of LH IL-6 resulted in a potent increase in sucrose-motivated behavior, without any effect on ingestive behavior or body weight in female rats. In contrast, the treatment did not affect any parameters measured (chow intake, sucrose-motivated behavior, locomotion, and body weight) in chow-fed males. However, when challenged with a high-fat/high-sugar diet, the male LH IL-6 knockdown rats displayed rapid weight gain and hyperphagia. Together, our data suggest that LH-produced IL-6 is necessary and sufficient for ingestive behavior and weight homeostasis in male rats. In females, IL-6 in the LH plays a critical role in food-motivated, but not ingestive behavior control or weight regulation. Thus, collectively these data support the idea that brain-produced IL-6 engages the hypothalamus to control feeding behavior. © 2021 The Authors
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| 9. |
- López-Ferreras, Lorena, et al.
(författare)
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Lateral hypothalamic GLP-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:5, s. 1157-1168
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Tidskriftsartikel (refereegranskat)abstract
- Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH. Ingestive behavior and metabolic parameters, as well as molecular and efferent targets, of the LH GLP-1R activation were also evaluated. Food motivation was reduced by activation of LH GLP-1R. Conversely, acute pharmacological blockade of LH GLP-1R increased food motivation but only in male rats. GLP-1R activation also induced a robust reduction in food intake and body weight. Chronic knockdown of LH GLP-1R induced by intraparenchymal delivery of an adeno-associated virus-short hairpin RNA construct was sufficient to markedly and persistently elevate ingestive behavior and body weight and ultimately resulted in a doubling of fat mass in males and females. Interestingly, increased food reinforcement was again found only in males. Our data identify the LH GLP-1R as an indispensable element of normal food reinforcement, food intake and body weight regulation. These findings also show, for we believe the first time, that brain GLP-1R manipulation can result in a robust and chronic body weight gain. The broader implications of these findings are that the LH differs between females and males in its ability to control motivated and ingestive behaviors.
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| 10. |
- López-Ferreras, Lorena, et al.
(författare)
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Sex-divergent effects of hindbrain GLP-1-producing neuron activation in rats
- 2023
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Ingår i: Frontiers in Neuroscience. - 1662-4548 .- 1662-453X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) analogs represent a new class of weight-loss medication, which has recently exponentially grown in popularity. GLP-1 is produced in the intestinal L cells in response to macronutrient intake, but it is also produced in the brain in a subset of neurons in the nucleus of the solitary tract (NTS). Exogenously-delivered GLP-1 analogs reduce food intake and food-motivated behavior in male and female rats, with some sex divergence of these effects in specific brain sites. These analogs potentially target GLP-1 receptors endogenously supplied by the gut and brain-produced GLP-1. The function of the NTS GLP-1-producing neurons [Gcg neurons] is still relatively unknown in rats. Moreover, even less is understood about the function of these neurons in females. We have recently developed a transgenic rat that expresses Cre under the Gcg promoter. Here, we interrogate this new animal model with optogenetics and chemogenetics to determine whether activation of the NTS GLP-1 neurons affects ingestive and motivated behavior in male and female rats. Optogenetic activation of the NTS Gcg neurons robustly reduced chow intake in both male and female rats. Interestingly, motivated behavior for a sucrose reward was reduced exclusively in females. To ensure that this unexpected sex difference was not activation method-specific, we next virally introduced excitatory DREADD receptors into the Gcg neurons and investigated the effect of chemogenetic activation of these neurons on ingestive and motivated behavior. Even upon chemogenetic activation, female rats reduced their motivation to obtain the sucrose reward, yet no effect on this behavior was observed in males. Our results show that activation of hindbrain Gcg neurons is sufficient to reduce food intake in both sexes. In females, but not males, Gcg neuron activation alone is also sufficient to reduce motivated behavior for sucrose. Thus, there is a sex difference in the ability of GLP-1-producing neuron activation to control motivated behavior for food.
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