The Brain Expresses the Insulin and Ins2+/- Mice Display Increased High-fat Food Intake

2012 ◽  
Vol 36 (5) ◽  
pp. S70
Author(s):  
Arya E. Mehran ◽  
Xiaoke Hu ◽  
G. Stefano Brigidi ◽  
Brad G. Hoffman ◽  
Shernaz X. Bamji ◽  
...  
Keyword(s):  
Food Intake ◽  
High Fat ◽  
The Brain

scholarly journals Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4745-4755 ◽  
Author(s):  
Dana I. Briggs ◽  
Pablo J. Enriori ◽  
Moyra B. Lemus ◽  
Michael A. Cowley ◽  
Zane B. Andrews
Keyword(s):  
Food Intake ◽  
High Fat Diet ◽  
Healthy Aging ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
High Fat ◽  
Appetite Control ◽  
Diet Induced Obesity ◽  
Therapeutic Outcomes ◽  
The Brain

Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not induce food intake in obese mice. We investigated whether ghrelin resistance was a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO) (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and decreasing expression of hypothalamic GHSR. Peripheral (ip) or central (intracerebroventricular) ghrelin injection was able to induce food intake and arcuate nucleus Fos immunoreactivity in chow-fed but not high-fat diet-fed mice. DIO decreased expression of Npy and Agrp mRNA, and central ghrelin was unable to promote expression of these genes. Ghrelin did not induce AgRP or NPY secretion in hypothalamic explants from DIO mice. Injection of NPY intracerebroventricularly increased food intake in both chow-fed and high-fat diet-fed mice, indicating that downstream NPY/AgRP neural targets are intact and that defective NPY/AgRP function is a primary cause of ghrelin resistance. Ghrelin resistance in DIO is not confined to the NPY/AgRP neurons, because ghrelin did not stimulate growth hormone secretion in DIO mice. Collectively, our data suggests that DIO causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis to limit further food intake. Ghrelin has a number of functions in the brain aside from appetite control, including cognitive function, mood regulation, and protecting against neurodegenerative diseases. Thus, central ghrelin resistance may potentiate obesity-related cognitive decline, and restoring ghrelin sensitivity may provide therapeutic outcomes for maintaining healthy aging.

scholarly journals High-Fat Diet-Induced Trefoil Factor Family Member 2 (TFF2) to Counteract the Immune-Mediated Damage in Mice

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 258
Author(s):  
Abdelaziz Ghanemi ◽  
Mayumi Yoshioka ◽  
Jonny St-Amand
Keyword(s):  
Food Intake ◽  
Family Member ◽  
Tissue Repair ◽  
Trefoil Factor ◽  
High Fat ◽  
Immune Mediated ◽  
Physiological Homeostasis ◽  
Immunological Reactions ◽  
Trefoil Factor Family ◽  
The Brain

Physiological homeostasis requires a balance between the immunological functions and the resulting damage/side effects of the immunological reactions including those related to high-fat (HF) diet. Within this context, whereas HF diet, through diverse mechanisms (such as inflammation), leads to immune-mediated damage, trefoil factor family member 2 (Tff2) represents a HF diet-induced gene. On the other hand, TFF2 both promotes tissue repair and reduces inflammation. These properties are towards counteracting the immune-mediated damage resulting from the HF diet. These observations suggest that the HF diet-induction of Tff2 could be a regulatory pathway aiming to counteract the immune-mediated damage resulting from the HF diet. Interestingly, since Tff2 expression increases with HF diet and with Tff2 also expressed in the brain, we also hypothesize that TFF2 could be a HF diet-induced food intake-control signal that reduces appetite. This hypothesis fits with counteracting the immune damage since reducing the food intake will reduce the HF intake and therefore, reduces the HF diet-induced tissue damage. Such food intake signaling would be an indirect mechanism by which TFF2 promotes tissue repair as well as a pathway worth exploring for potential obesity management pharmacotherapies.

scholarly journals Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet

2009 ◽  
Vol 296 (5) ◽  
pp. E1003-E1012 ◽  
Author(s):  
Kelly A. Posey ◽  
Deborah J. Clegg ◽  
Richard L. Printz ◽  
Jaeman Byun ◽  
Gregory J. Morton ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
Inflammatory Responses ◽  
Neuronal Response ◽  
Caloric Intake ◽  
Reduce Food Intake ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Regulate Food Intake ◽  
The Brain

Weight gain induced by an energy-dense diet is hypothesized to arise in part from defects in the neuronal response to circulating adiposity negative feedback signals, such as insulin. Peripheral tissue insulin resistance involves cellular inflammatory responses thought to be invoked by excess lipid. Therefore, we sought to determine whether similar signaling pathways are activated in the brain of rats fed a high-fat (HF) diet. The ability of intracerebroventricular (icv) insulin to reduce food intake and activate hypothalamic signal transduction is attenuated in HF-fed compared with low-fat (LF)-fed rats. This effect was accompanied by both hypothalamic accumulation of palmitoyl- and stearoyl-CoA and activation of a marker of inflammatory signaling, inhibitor of κB kinase-β (IKKβ). Hypothalamic insulin resistance and inflammation were observed with icv palmitate infusion or HF feeding independent of excess caloric intake. Last, we observed that central IKKβ inhibition reduced food intake and was associated with increased hypothalamic insulin sensitivity in rats fed a HF but not a LF diet. These data collectively support a model of diet-induced obesity whereby dietary fat, not excess calories, induces hypothalamic insulin resistance by increasing the content of saturated acyl-CoA species and activating local inflammatory signals, which result in a failure to appropriately regulate food intake.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

scholarly journals High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

2021 ◽  
Vol 22 (7) ◽  
pp. 3746
Author(s):  
Ilaria Zuliani ◽  
Chiara Lanzillotta ◽  
Antonella Tramutola ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Hexosamine Biosynthetic Pathway ◽  
Neurodegenerative Process ◽  
The Brain

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

scholarly journals Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun Lim ◽  
Seolsong Kim ◽  
Eun-Kyoung Kim
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Fat ◽  
Selective Autophagy ◽  
Induced Stress ◽  
Hypothalamic Cells ◽  
The Brain ◽  
Main Region

AbstractPalmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism. Interestingly, hypothalamic palmitate level is also increased under starvation, urging the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, we show that ER-phagy (ER-targeted selective autophagy) is required for progress of ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that, unlike the induction of ER stress under nutrient-rich conditions, palmitate protects hypothalamic cells from starvation-induced stress by inhibiting ER-phagy.

scholarly journals Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 940
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Shuai Zhu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Behavioral Performance ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Obeticholic Acid ◽  
Promising Agent ◽  
Serum Biochemical ◽  
Lipid Metabolites ◽  
The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

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