High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice

Bales, Michelle B.; Centanni, Samuel W.; Luchsinger, Joseph R.; Fathi, Payam; Biddinger, Jessica E.; Le, Thao D. V.; Nwaba, Kaitlyn Ginika; Winder, Danny G.; Ayala, Julio E.

doi:10.1016/j.molmet.2022.101571

Cited by 7 publications

(3 citation statements)

References 63 publications

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“…To further confirm the apparent toxicity of the AAV-Cre that we used, we tested it in another brain region: the dorsal lateral septum (dLS). The glucagon-like peptide-1 receptor (GLP-1R) is highly expressed in dLS and is implicated in feeding and metabolism (30)(31)(32)(33). We assessed if a diluted AAV-Cre could be used to determine endogenous GLP-1R function.…”

Section: Delivery Of Aav-mediated Cre In the Dorsolateral Septum Indu...mentioning

confidence: 99%

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus

Savani,

Park,

Busannagari

et al. 2023

Preprint

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ObjectiveCombining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research in diverse cell types and tissues using AAV-Cre exemplifies advantages over crossing with Cre driver lines in several aspects, including saving time and avoiding developmental/compensatory issues. We initially sought to study the impact of ablation of corticotropin-releasing hormone (CRH) in the paraventricular hypothalamic nucleus (PVN) using intracranial AAV8-hSyn-Cre injection in adult animals.MethodsIn this study, we stereotactically injected AAV8-hSyn-Cre or a control viral vector (1E13 and 1E12 vg/ml, respectively, both at 150 nL) in both Crh-floxed and wild-type mouse PVN to assess behavioral and metabolic impacts. We then used immunohistochemical markers to systematically evaluate the density of hypothalamic peptidergic neurons and glial cells.ResultsWe found that delivery of one preparation of AAV8-hSyn-Cre in the PVN led to the development of obesity, hyperphagia, and anxiety-like behaviors. This effect occurred independent of sex and in both floxed and wild-type mice. We subsequently found that AAV8-hSyn-Cre led to neuronal cell death and gliosis at the site of viral vector injections. These behavioral and metabolic deficits were dependent on injection into the PVN specifically.ConclusionsOur findings reveal that delivery of AAV8-hSyn-Cre could lead to cellular toxicity and lesions in the PVN that cause robust metabolic and behavioral impacts. These alterations can complicate the interpretation of AAV-Cre-mediated gene knockout and highlight the need for rigorous controls.

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Section: Delivery Of Aav-mediated Cre In the Dorsolateral Septum Indu...mentioning

confidence: 99%

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus

Savani,

Park,

Busannagari

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Regard to neuropeptide systems that could regulate the activity of LS neurons, it has been shown that LS microinjection of GLP-1 decreases control food intake, while LS microinjections of antagonists of GLP-1 receptors only increases palatable food intake ( Terrill et al, 2019 ). Recently, it has been shown that acute restraint stress increases the activity of LS neurons that express the GLP-1 receptor, decreasing food intake in male mice fed a control diet ( Bales et al, 2022 ). However, in obese male mice the restraint stress does not increase the activity of LS GLP-1R neurons or produce hypophagia ( Bales et al, 2022 ).…”

Section: Lateral Septum and Feedingmentioning

confidence: 99%

“…Recently, it has been shown that acute restraint stress increases the activity of LS neurons that express the GLP-1 receptor, decreasing food intake in male mice fed a control diet ( Bales et al, 2022 ). However, in obese male mice the restraint stress does not increase the activity of LS GLP-1R neurons or produce hypophagia ( Bales et al, 2022 ). Finally, the LS microinjection of μ-receptor agonists such as morphine and DAMGO reduces and increases the latency to eat and food intake, respectively ( Calderwood et al, 2022 ).…”

Section: Lateral Septum and Feedingmentioning

confidence: 99%

Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity

Olivares-Barraza

Marcos²,

Martínez-Pinto³

et al. 2022

Front. Mol. Neurosci.

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Obesity is a pandemic associated with lifestyles changes. These include excess intake of obesogenic foods and decreased physical activity. Brain areas, like the lateral hypothalamus (LH), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been linked in both homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. Interestingly, these control systems are regulated by the lateral septum (LS), a relay of γ-aminobutyric (GABA) acid neurons (GABAergic neurons) that inhibit the LH and GABAergic interneurons of the VTA. Furthermore, the LS has a diverse receptor population for neurotransmitters and neuropeptides such as dopamine, glutamate, GABA and corticotropin-releasing factor (CRF), among others. Particularly, CRF a key player in the stress response, has been related to the development of overweight and obesity. Moreover, evidence shows that LS neurons neurophysiologically regulate reward and stress, although there is little evidence of LS taking part in homeostatic and hedonic feeding. In this review, we discuss the evidence that supports the role of LS and CRF on feeding, and how alterations in this system contribute to weight gain obesity.

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The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity

Laughlin,

McIndoe,

Adams

et al. 2024

Mamm Genome

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The Mouse Metabolic Phenotyping Center (MMPC)Live Program was established in 2023 by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high quality phenotyping services for mouse models of diabetes and obesity. Emerging as the next iteration of the MMPC Program which served the biomedical research community for 20 years (2001–2021), MMPCLive is designed as an outwardly-facing consortium of service cores that collaborate to provide reduced-cost consultation and metabolic, physiologic, and behavioral phenotyping tests on live mice for U.S. biomedical researchers. Four MMPCLive Centers located at universities around the country perform complex and often unique procedures in vivo on a fee for service basis, typically on mice shipped from the client or directly from a repository or vendor. Current areas of expertise include energy balance and body composition, insulin action and secretion, whole body carbohydrate and lipid metabolism, cardiovascular and renal function, food intake and behavior, microbiome and xenometabolism, and metabolic pathway kinetics. Additionally, an opportunity arose to reduce barriers to access and expand the diversity of the biomedical research workforce by establishing the VIBRANT Program. Directed at researchers historically underrepresented in the biomedical sciences, VIBRANT-eligible investigators have access to testing services, travel and career development awards, expert advice and experimental design consultation, and short internships to learn test technologies. Data derived from experiments run by the Centers belongs to the researchers submitting mice for testing which can be made publicly available and accessible from the MMPCLive database following publication. In addition to services, MMPCLive staff provide expertise and advice to researchers, develop and refine test protocols, engage in outreach activities, publish scientific and technical papers, and conduct educational workshops and training sessions to aid researchers in unraveling the heterogeneity of diabetes and obesity.

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High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice

Cited by 7 publications

References 63 publications

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus

Corticotropin-releasing factor system in the lateral septum: Implications in the pathophysiology of obesity

The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity

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