High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats

Noronha, Sylvana Rendeiro de; Campos, Glenda; Abreu, Aline Rezende; Souza, Aline Maria Arlindo de; Chianca, Deoclécio A.; Menezes, Rodrigo Cunha Alvim de

doi:10.1016/j.bbr.2016.08.042

Cited by 58 publications

(36 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This relationship has also been demonstrated in obese mice fed a HFD 30, 31 , which also displayed functional alterations and neural adaptations in GABAergic dorsomedial hypothalamic neurons and brain reward circuitry, respectively. Previous studies have suggested that LH-21 has lower BBB permeability than other CB1 antagonists, like rimonabant, and that acute effects of LH-21 on feeding are not associated with anxiety-like behaviours 12, 15 .…”

Section: Discussionmentioning

confidence: 66%

“…Interestingly, as stated above, we have recently found that some metabolic actions of LH-21 could be mediated through GPR55 17 , and this receptor is also known to be expressed at the central nervous system 25, 26, 33 . Specifically, the nucleus accumbens and the hypothalamus are among the brain regions with higher GPR55 expression 25, 26 , both of them being involved in anxiogenesis 30, 31 . Thus, anxiety-related effects of LH-21 could be mediated through central GPR55 receptors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice

Romero-Zerbo

Ruz‐Maldonado

Espinosa-Jímenez

et al. 2017

Sci Rep

View full text Add to dashboard Cite

LH-21 is a triazol derivative that has been described as a low-permeant neutral CB1 antagonist, though its pharmacology is still unclear. It has been associated with anti-obesity actions in obese rats. However, its role in preventing type 2 diabetes (T2D) onset have not been studied yet. Given CB1 receptors remain as potential pharmacological targets to fight against obesity and T2D, we wanted to explore the metabolic impact of this compound in an animal model of obesity and pre-diabetes as well as the lack of relevant actions in related central processes such as anxiety. C57BL/6J mice were rendered obese and pre-diabetic by feeding a high-fat diet for 15 weeks and then treated with LH-21 or vehicle for two weeks. Food intake, body weight and glucose handling were assessed, together with other relevant parameters. Behavioural performance was evaluated by the open field test and the elevated plus maze. LH-21 did not affect food intake nor body weight but it improved glucose handling, displaying tissue-specific beneficial actions. Unexpectedly, LH-21 induced anxiolysis and reverted obesity-induced anxiety, apparently through GPR55 receptor. These results suggest that LH-21 can be a new candidate to fight against diabetes onset. Indeed, this compound shows potential in counteracting obesity-related anxiety.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice

Romero-Zerbo

Ruz‐Maldonado

Espinosa-Jímenez

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…HFD‐induced obesity facilitates anxiety in rats . Therefore, we examined whether HFD could cause anxiety‐like behaviors in mice ( Figure a–c).…”

Section: Resultsmentioning

confidence: 99%

Lactobacillus sakei Alleviates High‐Fat‐Diet‐Induced Obesity and Anxiety in Mice by Inducing AMPK Activation and SIRT1 Expression and Inhibiting Gut Microbiota‐Mediated NF‐κB Activation

Jang

Han

Kim

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Long‐term feeding of a high‐fat diet (HFD) causes gastrointestinal inflammation and gut microbiota disturbance, leading to the increased occurrence of obesity and anxiety. In the present study, the effects of heat‐labile Lactobacillus sakei OK67, tyndallized OK67 (tOK67), and heat‐stable Lactobacillus sakei PK16 on HFD‐induced obesity and anxiety in mice are examined. Methods and results Obesity is induced in mice by feeding with HFD. Oral administration of live OK67, tOK67, or PK16 reduces HFD‐induced body and liver weights and blood triglyceride, total cholesterol, corticosterone, and lipopolysaccharide levels. These treatments also suppress HFD‐induced NF‐κB activation and increased HFD‐suppressed AMP‐activated protein kinase (AMPK) activation and SIRT‐1 expression in the liver. OK67 or PK16 treatment alleviates HFD‐induced anxiety‐like behaviors and increases BDNF expression and NF‐κB activation in the hippocampus. Moreover, OK67 or PK16 treatment suppresses HFD‐induced colitis and suppresses the Proteobacteria population and fecal lipopolysaccharide levels in mice. OK67 or PK16 treatment inhibits NF‐κB activation and induced AMPK activation and SIRT‐1 expression in lipopolysaccharide‐stimulated Caco‐2 cells. Overall, the antiobesity and anxiolytic effects of live OK67 are more potent than those of tOK67. Conclusion Lactobacillus sakei can alleviate HFD‐induced obesity, colitis, and anxiety by regulating gut microbiota‐mediated AMPK and NF‐κB activation and SIRT‐1 expression.

show abstract

“…It will be interesting to investigate whether hypothalamic BDNF's modulation of the HPA axis contributes to the anti‐depression effect in the aged animals whose stress response system becomes less agile and dysfunctional. Although no change in BDNF expression was found in either the hippocampus or the amygdala, it is still possible that global improvement of metabolism induced by hypothalamic BDNF overexpression indirectly influences other limbic structures, including the prefrontal cortex, hippocampus, nucleus accumbens, ventral striatum, amygdala, and hypothalamus (Russo, Murrough, Han, Charney, & Nestler, ) and thereby affects brain functions and behaviors (de Noronha et al, ).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

et al. 2018

View full text Add to dashboard Cite

The aging process and age‐related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet‐induced and genetic models. Here we examined the efficacy and safety of a built‐in autoregulatory system to control transgene BDNF expression mimicking the body's natural feedback systems in middle‐aged mice. Twelve‐month‐old mice were treated with either autoregulatory BDNF vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. BDNF gene transfer prevented the development of aging‐associated metabolic declines characterized by: preventing aging‐associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, BDNF treatment reduced anxiety‐like and depression‐like behaviors. These safety and efficacy data provide evidence that hypothalamic BDNF is a target for promoting healthy aging.

show abstract

High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats

Cited by 58 publications

References 51 publications

The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice

The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice

Lactobacillus sakei Alleviates High‐Fat‐Diet‐Induced Obesity and Anxiety in Mice by Inducing AMPK Activation and SIRT1 Expression and Inhibiting Gut Microbiota‐Mediated NF‐κB Activation

Hypothalamic gene transfer of BDNF promotes healthy aging in mice

Contact Info

Product

Resources

About