The effect of metformin on neuronal activity in the appetite-regulating brain regions of mice fed a high-fat diet during an anorectic period

2016 ◽  
Vol 154 ◽  
pp. 184-190 ◽  
Author(s):  
Hyun-Ju Kim ◽  
Bo-Yeong Jin ◽  
Mi-Jeong Oh ◽  
Kyung-Ho Shin ◽  
Sang-Hyun Choi ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
High Fat Diet ◽  
Brain Regions ◽  
High Fat

scholarly journals Metformin Treatment Attenuates Brain Inflammation and Rescues Pacap/Vip Neuropeptide Alterations in Mice Fed a High-Fat Diet

2021 ◽  
Vol 22 (24) ◽  
pp. 13660
Author(s):  
Mawj Mandwie ◽  
Jocelyn Karunia ◽  
Aram Niaz ◽  
Kevin A. Keay ◽  
Giuseppe Musumeci ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Brain Inflammation ◽  
Low Grade ◽  
Metformin Treatment ◽  
High Fat ◽  
Activation Markers ◽  
Beneficial Effects ◽  
Therapeutic Activities

High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin’s therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT(Ser473) expression and caused significant disruptions to the PACAP/VIP system. Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD. Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis. Data also suggests that the PI3K/AKT pathway, at least in part, mediates some of metformin’s beneficial effects.

scholarly journals Effects of Food Deprivation and High Fat Diet on Immunoreactive .BETA.-Endrophin Levels in Brain Regions of Zucker Rats.

1987 ◽  
Vol 34 (6) ◽  
pp. 903-909 ◽  
Author(s):  
SATORU TSUJII ◽  
YOSHIKATSU NAKAI ◽  
JUNICHI FUKATA ◽  
SHIGEO NAKAISHI ◽  
HIDEO TAKAHASHI ◽  
...  
Keyword(s):  
Food Deprivation ◽  
High Fat Diet ◽  
Brain Regions ◽  
Zucker Rats ◽  
High Fat

scholarly journals Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions

2009 ◽  
Vol 117 (6) ◽  
pp. 916-922 ◽  
Author(s):  
Theodore A. Slotkin ◽  
T. Leon Lassiter ◽  
Ian T. Ryde ◽  
Nicola Wrench ◽  
Edward D. Levin ◽  
...  
Keyword(s):  
Rat Brain ◽  
High Fat Diet ◽  
Brain Regions ◽  
High Fat ◽  
Rat Brain Regions

Behavioral changes in male mice fed a high-fat diet are associated with IL-1β expression in specific brain regions

2017 ◽  
Vol 169 ◽  
pp. 130-140 ◽  
Author(s):  
Camila P. Almeida-Suhett ◽  
Alice Graham ◽  
Yifan Chen ◽  
Patricia Deuster
Keyword(s):  
High Fat Diet ◽  
Brain Regions ◽  
Behavioral Changes ◽  
Male Mice ◽  
High Fat

Abstract P181: Contrasting Effects of High Fat Diet and DOCA-salt on Primary Neuronal Cilia

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Jingwei Jiang ◽  
Kamal Rahmouni
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Cardiovascular Regulation ◽  
Brain Regions ◽  
Normal Diet ◽  
High Fat ◽  
Pronounced Difference ◽  
Software Analysis ◽  
Neuronal Cilia ◽  
The Brain

Virtually, every mammalian cell is equipped with an antenna like primary cilium, a cell surface protrusion that is thought to act as a sensory organelle. Many of the rare genetic disorders that cause shorter, absent or disrupted cilia are associated with obesity and cardiovascular dysfunction in humans and rodents, which suggest that cilia length contribute to energy balance and cardiovascular homeostasis. Here, we examined the length of the primary neuronal cilia in the brain nuclei that contribute to metabolic and cardiovascular regulation in high fat diet-induced obese (DIO) mice and DOCA-salt mice. Cilia length was examined by adenylate cyclase 3 (AC3) immunostaining, followed by confocal 3D reconstruction, and quantification by IMARIS imaging analysis software. Analysis of the cilia length and distribution showed reduced frequency of cilia that are over 10 μm in the brain of DIO mice compared to control mice fed normal diet fed mice (17.02±1.36% vs 23.78±1.15%, p=0.032). Interestingly, the most pronounced difference in cilia length was observed in the dorsomedial hypothalamus with the DIO mice displaying significantly shorter cilia (6.90±0.06 μm) relative to controls (7.32±0.14μm in controls, n=5/group p<0.05). Conversely, we found that average neuronal cilia length was elongated in 3-week DOCA-salt treated mice compared to sham group. The number of primary neuronal cilia that are over 10 μm was significantly increased in DOCA-salt mice by 8% (p=0.0114). On the other hand, the number of cilia that are 4-5 μm in length was significantly decreased in DOCA-salt mice compared to sham controls (11.73±1.70% vs 18.73±2.02%, p=0.0385). The supraoptic nucleus was the only nucleus that displayed difference in the length of cilia that are 5-10 μm in length (7.46±0.24 μm vs 6.76±0.15μm, n=5/group, p=0.0509). Our data demonstrate plasticity of neuronal cilia in response to high fat diet and DOCA-salt treatment in defined brain regions. Our results raise the possibility that primary neuronal cilia may function as part of environmental surveillance system in the brain that control energy homeostasis and cardiovascular function. Further analysis of the role of primary neuronal cilia in cardiovascular regulation is underway.

scholarly journals Neonatal parathion exposure disrupts serotonin and dopamine synaptic function in rat brain regions: Modulation by a high-fat diet in adulthood

2009 ◽  
Vol 31 (6) ◽  
pp. 390-399 ◽  
Author(s):  
Theodore A. Slotkin ◽  
Nicola Wrench ◽  
Ian T. Ryde ◽  
T. Leon Lassiter ◽  
Edward D. Levin ◽  
...  
Keyword(s):  
Rat Brain ◽  
High Fat Diet ◽  
Brain Regions ◽  
Synaptic Function ◽  
High Fat ◽  
Rat Brain Regions

High fat diet increases the incidence of orofacial dyskinesia and oxidative stress in specific brain regions of rats

2005 ◽  
Vol 81 (3) ◽  
pp. 585-592 ◽  
Author(s):  
R FACHINETTO ◽  
M BURGER ◽  
C WAGNER ◽  
D WONDRACEK ◽  
V BRITO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Brain Regions ◽  
High Fat ◽  
Orofacial Dyskinesia ◽  
And Oxidative Stress

scholarly journals Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4880-4889 ◽  
Author(s):  
Heike Münzberg ◽  
Jeffrey S. Flier ◽  
Christian Bjørbæk
Keyword(s):  
High Fat Diet ◽  
Leptin Receptor ◽  
Elevated Serum ◽  
Brain Regions ◽  
Leptin Resistance ◽  
Hypothalamic Nucleus ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
High Fat ◽  
Suppressor Of Cytokine Signaling

Abstract Leptin resistance in diet-induced obese (DIO) mice is characterized by elevated serum leptin and a decreased response to exogenous leptin and is caused by unknown defects in the central nervous system. Leptin normally acts on several brain nuclei, but a detailed description of leptin resistance within individual brain regions has not been reported. We first mapped leptin-responsive cells in brains from DIO mice using phospho-signal transducer and activator of transcription (P-STAT3) immunohistochemistry. After 16 wk of high-fat-diet feeding, leptin-activated P-STAT3 staining within the arcuate nucleus (ARC) was dramatically decreased. In contrast, other hypothalamic and extrahypothalamic nuclei remained leptin sensitive. Reduced leptin-induced P-STAT3 in the ARC could also be detected after 4 wk and as early as 6 d of a high-fat diet. To examine potential mechanisms for leptin-resistant STAT3 activation in the ARC of DIO mice, we measured mRNA levels of candidate signaling molecules in the leptin receptor-STAT3 pathway. We found that the level of suppressor of cytokine signaling 3 (SOCS-3), an inhibitor of leptin signaling, is specifically increased in the ARC of DIO mice. The study suggests that the ARC is selectively leptin resistant in DIO mice and that this may be caused by elevated suppressor of cytokine signaling 3 in this hypothalamic nucleus. Defects in leptin action in the ARC may play a role in the pathogenesis of leptin-resistant obesity.

scholarly journals Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs

2019 ◽  
Vol 116 (21) ◽  
pp. 10547-10556 ◽  
Author(s):  
Gitalee Sarker ◽  
Wenfei Sun ◽  
David Rosenkranz ◽  
Pawel Pelczar ◽  
Lennart Opitz ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Small Rnas ◽  
Drugs Of Abuse ◽  
Brain Regions ◽  
High Fat ◽  
Potential Vector ◽  
Paternal Lineage ◽  
Metabolic Phenotypes ◽  
Enhanced Sensitivity ◽  
Maternal Overnutrition

There is a growing body of evidence linking maternal overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently, we demonstrated in a maternal high-fat diet (HFD; MHFD) mouse model that MHFD induced enhanced hedonic behaviors and obesogenic phenotypes that were conserved across three generations via the paternal lineage, which was independent of sperm methylome changes. Here, we show that sperm tRNA-derived small RNAs (tsRNAs) partly contribute to the transmission of such phenotypes. We observe increased expression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection of sperm tsRNAs from the F1-HFD male into normal zygotes reproduces obesogenic phenotypes and addictive-like behaviors, such as increased preference of palatable foods and enhanced sensitivity to drugs of abuse in the resultant offspring. The expression of several of the differentially expressed sperm tsRNAs predicted targets such as CHRNA2 and GRIN3A, which have been implicated in addiction pathology, are altered in the mesolimbic reward brain regions of the F1-HFD father and the resultant HFD-tsRNA offspring. Together, our findings demonstrate that sperm tsRNA is a potential vector that contributes to the transmission of MHFD-induced addictive-like behaviors and obesogenic phenotypes across generations, thereby emphasizing its role in diverse pathological outcomes.

scholarly journals Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Darren J. Fernandes ◽  
Shoshana Spring ◽  
Anna R. Roy ◽  
Lily R. Qiu ◽  
Yohan Yee ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Early Life ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Long Term Effects ◽  
High Fat ◽  
Reward Seeking ◽  
Low Fat Diet ◽  
Increased Risk ◽  
Fat Diets

AbstractMaternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.

Sign in / Sign up

Export Citation Format

Share Document