scholarly journals Chronic administration of brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reverses obesity induced by high-fat diet

2010 ◽  
Vol 298 (5) ◽  
pp. R1320-R1332 ◽  
Author(s):  
ChuanFeng Wang ◽  
Rebecca J. Godar ◽  
Charles J. Billington ◽  
Catherine M. Kotz
Keyword(s):  
Body Weight ◽  
Body Fat ◽  
Paraventricular Nucleus ◽  
Neurotrophic Factor ◽  
High Fat Diet ◽  
Control Diet ◽  
Brain Derived Neurotrophic Factor ◽  
Hypothalamic Paraventricular Nucleus ◽  
High Fat ◽  
Metabolic Indices

An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic paraventricular nucleus (PVN) reduces body weight by decreasing feeding and increasing energy expenditure (EE), in animals on standard laboratory chow. Animals have divergent responses to a high-fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study, we tested two hypotheses: 1) BDNF in the PVN reverses HFD-induced obesity, and 2) animals with higher body fat have a greater physiological response to BDNF than those with less body fat. Eighty-four 10-wk old rats were allowed HFD ad libitum for 9 wk and then prepared with bilateral PVN cannulas. Animals were then divided into tertiles based on their body fat rank: high, intermediate, and low (H, I, and L). Each group was further divided into 2 subgroups and then PVN injected with BDNF or control (artificial cerebrospinal fluid, aCSF) every other day for 3 wk. Energy intake (EI), body weight, and body composition were measured. At study's end, rats were killed to allow measurement of other metabolic indices. In parallel, another 12 rats were fed control diet (CD), PVN-cannulated and injected with aCSF. HFD exposure induced obesity, particularly in the H body fat group, with a significant increase in EI, body weight, fat mass, liver size, and serum glucose, triglycerides, insulin, and leptin. BDNF significantly reduced EI, body weight, body fat, lean mass, and serum metabolic indices. These BDNF effects were greatest in the H body fat group. These data indicate that BDNF reduced HFD-induced obesity and metabolic syndrome-like measures, and the animals with the most body fat had the most significant response to BDNF.

Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reduces energy intake

2007 ◽  
Vol 293 (3) ◽  
pp. R1003-R1012 ◽  
Author(s):  
ChuanFeng Wang ◽  
Eric Bomberg ◽  
Charles Billington ◽  
Allen Levine ◽  
Catherine M. Kotz
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Paraventricular Nucleus ◽  
Neurotrophic Factor ◽  
Body Weight Gain ◽  
Brain Derived Neurotrophic Factor ◽  
Brain Regions ◽  
Hypothalamic Paraventricular Nucleus ◽  
Bdnf Mrna ◽  
Hypothalamic Arcuate Nucleus

Recent studies show that brain-derived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor tyrosine kinase B (TrkB) are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF in the hypothalamic paraventricular nucleus (PVN) on feeding. BDNF injected unilaterally or bilaterally into the PVN of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0- to 24-h and 24- to 48-h postinjection intervals. Effective doses producing inhibition of feeding behavior did not establish a conditioned taste aversion. PVN BDNF significantly decreased PVN neuropeptide Y (NPY)-induced feeding at 1, 2, and 4 h following injection. BDNF administration in the PVN abolished food-restriction-induced NPY gene expression in the hypothalamic arcuate nucleus. In conclusion, BDNF in the PVN significantly decreases food intake and body weight gain, suggesting that the PVN is an important site of action for BDNF in its effects on energy metabolism. Furthermore, BDNF appears to interact with NPY in its anorectic actions, although a direct effect on NPY remains to be established.

scholarly journals Impaired CNS Leptin Action Is Implicated in Depression Associated with Obesity

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2634-2643 ◽  
Author(s):  
Nobuko Yamada ◽  
Goro Katsuura ◽  
Yukari Ochi ◽  
Ken Ebihara ◽  
Toru Kusakabe ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
High Fat Diet ◽  
Control Diet ◽  
Preference Test ◽  
Antidepressant Activity ◽  
Brain Derived Neurotrophic Factor ◽  
Epidemiological Studies ◽  
High Fat ◽  
Depressive Behavior ◽  
Sucrose Preference Test

Recent epidemiological studies indicate that obesity increases the incidence of depression. We examined the implication of leptin for obesity-associated depression. Leptin induced antidepressive behavior in normal mice in a forced swimming test (FST), and leptin-overexpressing transgenic mice with hyperleptinemia exhibited more antidepressive behavior in the FST than nontransgenic mice. In contrast, leptin-deficient ob/ob mice showed more severe depressive behavior in the FST than normal mice, and leptin administration substantially ameliorated this depressive behavior. Diet-induced obese (DIO) mice fed a high-fat diet showed more depressive behavior in the FST and in a sucrose preference test compared with mice fed a control diet (CD). In DIO mice, leptin induced neither antidepressive action nor increment of the number of c-Fos immunoreactive cells in the hippocampus. Diet substitution from high-fat diet to CD in DIO mice ameliorated the depressive behavior and restored leptin-induced antidepressive action. Brain-derived neurotrophic factor concentrations in the hippocampus were significantly lower in DIO mice than in CD mice. Leptin administration significantly increased hippocampal brain-derived neurotrophic factor concentrations in CD mice but not in DIO mice. The antidepressant activity of leptin in CD mice was significantly attenuated by treatment with K252a. These findings demonstrated that leptin induces an antidepressive state, and DIO mice, which exhibit severe depressive behavior, did not respond to leptin in both the FST and the biochemical changes in the hippocampus. Thus, depression associated with obesity is due, at least in part, to impaired leptin activity in the hippocampus.

Brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus increases energy expenditure by elevating metabolic rate

2007 ◽  
Vol 293 (3) ◽  
pp. R992-R1002 ◽  
Author(s):  
ChuanFeng Wang ◽  
Eric Bomberg ◽  
Charles Billington ◽  
Allen Levine ◽  
Catherine M. Kotz
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Paraventricular Nucleus ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Hypothalamic Paraventricular Nucleus ◽  
Sites Of Action

Brain-derived neurotrophic factor (BDNF) decreases food intake and body weight, but few central sites of action have been identified. The hypothalamic paraventricular nucleus (PVN) is important in energy metabolism regulation, and expresses both BDNF and its receptor. We tested three hypotheses: 1) PVN BDNF reduces feeding and increases energy expenditure (EE), 2) PVN BDNF-enhanced thermogenesis results from increased spontaneous physical activity (SPA) and resting metabolic rate (RMR), and 3) PVN BDNF thermogenic effects are mediated, in part, by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). BDNF (0.5 μg) was injected into the PVN of Sprague-Dawley rats; and oxygen consumption, carbon dioxide production, food intake, and SPA were measured for 24 h in an indirect calorimeter. SPA was also measured in open-field activity chambers for 48 h after BDNF injection. Animals were killed 6 or 24 h after BDNF injection, and BAT UCP1 gene expression was measured with quantitative real-time PCR. BDNF significantly decreased food intake and body weight gain 24 h after injection. Heat production and RMR were significantly elevated for 7 h immediately after BDNF injection. BDNF had no effect on SPA, but increased UCP1 gene expression in BAT at 6 h, but not 24 h after injection. In conclusion, PVN BDNF reduces body weight by decreasing food intake and increasing EE consequent to increased RMR, which may be due, in part, to BAT UCP1 activity. These data suggest that the PVN is an important site of BDNF action to influence energy balance.

scholarly journals Effect of selective expression of dominant-negative PPARγ in pro-opiomelanocortin neurons on the control of energy balance

2016 ◽  
Vol 48 (7) ◽  
pp. 491-501 ◽  
Author(s):  
Madeliene Stump ◽  
Deng-Fu Guo ◽  
Ko-Ting Lu ◽  
Masashi Mukohda ◽  
Xuebo Liu ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
High Fat Diet ◽  
Control Diet ◽  
Cre Recombinase ◽  
Dominant Negative ◽  
High Fat ◽  
Pparγ Agonist ◽  
The Brain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

scholarly journals Pyroglutamyl leucine, a peptide in fermented foods, attenuates dysbiosis by increasing host antimicrobial peptide

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Saki Shirako ◽  
Yumi Kojima ◽  
Naohiro Tomari ◽  
Yasushi Nakamura ◽  
Yasuki Matsumura ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Administration ◽  
Antimicrobial Peptide ◽  
High Fat Diet ◽  
Control Diet ◽  
Experimental Colitis ◽  
Fermented Foods ◽  
Food Protein ◽  
High Fat ◽  
Tryptic Fragment

Abstract PyroGlu-Leu is present in certain food protein hydrolysates and traditional Japanese fermented foods. Our previous study demonstrated that the oral administration of pyroGlu-Leu (0.1 mg/kg body weight) attenuates dysbiosis in mice with experimental colitis. The objective of this study was to elucidate why such a low dose of pyroGlu-Leu attenuates dysbiosis in different animal models. High fat diet extensively increased the ratio of Firmicutes/Bacteroidetes in feces of rats compared to control diet. Oral administration of pyroGlu-Leu (1 mg/kg body weight) significantly attenuated high fat diet-induced dysbiosis. By focusing on the production of intestinal antimicrobial peptides, we found that pyroGlu-Leu significantly increased the level of 4962 Da peptides, which identified as the propeptide of rattusin or defensin alpha 9, in ileum. We also observed increased tryptic fragment peptides from rattusin in the lumen. Here, we report that orally administered pyroGlu-Leu attenuates dysbiosis by increasing in the host antimicrobial peptide, rattusin.

The effect of a high-fat diet and sucrose drinking option on the development of obesity in spontaneously hypertensive rats

1986 ◽  
Vol 56 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Stephen Rattigan ◽  
Peter R.C. Howe ◽  
Michael G. Clark
Keyword(s):  
Body Weight ◽  
Body Fat ◽  
High Fat Diet ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Spontaneously Hypertensive ◽  
Total Body Fat ◽  
Total Body ◽  
Sucrose Drinking ◽  
Starch Diet

1. Energy intakes, body-weights, body fat index, total body fat and interscapular brown adipose tissue (IBAT) were examined in adult male, spontaneously hypertensive, stroke-prone (SHR-SP) rats and normotensive Wistar/Kyoto (WKY) controls given one of four diets for 33 d: (a) a starch diet, (b) a starch diet and a sucrose solution drinking option, (c) an 80xenergy from fat (F80) diet, (d) the F80 diet and a sucrose drinking option.2. The SHR-SP rats showed a complete resistance to obesity on all four diets. For the high-fat diet the WKY animals became markedly obese with approximately two-fold increases in body-weight gain and body fat index when compared with the SHR-SP rats. The gain in total body fat was also significantly greater. IBAT as a percentage of total body-weight did not differ between the WKY and SHR-SP groups.3. Compared with the WKY animals, the SHR-SP rats showed a reduced food intake but had the same potential to gain weight from the high-fat diet.4. It is concluded that the resistance to obesity by the hypertensive animals is the result of a diminished energy intake.

scholarly journals Effects of Omega-3 Fatty Acids on Insulin Resistance in an Ovariectomized Mouse Model of Diet-Induced Obesity Treated with Chemotherapy

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 345-345
Author(s):  
Kate Ormiston ◽  
Zihan Zhang ◽  
Kelly Murphy ◽  
A Courtney DeVries ◽  
Maryam Lustberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Blood Glucose ◽  
Body Fat ◽  
High Fat Diet ◽  
Serum Insulin ◽  
Model Assessment ◽  
Omega 3 ◽  
High Fat ◽  
Body Weights

Abstract Objectives Our objective was to examine effects of dietary enrichment of eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) on high fat diet-induced insulin resistance during chemotherapy. Methods Adult, female C57Bl/6 mice (n = 48) were assigned to 1 of 3 diets; low-fat diet (LF; 10% kcals fat), high-fat diet (HF; 45% kcals fat), or HF diet with omega-3 s (HF n-3; 2% kcals EPA + DHA) for 7 weeks. Mice received vehicle or chemotherapy injections (doxorubicin + cyclophosphamide), by tail vein at week 4 and 6. Food intake and body weights were recorded. Fasted blood glucose and serum insulin were measured weekly.  Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Body composition was measured using Echo MRI. Data were analyzed using ANOVA; p < 0.05 was considered significant. Results Total kilocalories significantly differed by group (p < 0.001); HF and HF n-3 groups consumed more than the LF group (p < 0.001, p < 0.0001; respectively). Obesity was induced prior to first injection with body weights being significantly different (p < 0.01); the LF group weighed less than the HF n-3 group (p < 0.01), and there was a similar trend between LF and HF groups (p = 0.0519). Body weights at sacrifice significantly differed (p < 0.0001); chemotherapy mice weighed less than vehicle (p < 0.0001). Percent body fat at sacrifice significantly differed (p < 0.0001); chemotherapy mice had less fat than vehicle (p < 0.0001), and the LF group had less fat than HF  (p < 0.01) and HF n-3 group (p < 0.01). Blood glucose significantly differed at sacrifice (p < 0.01); chemotherapy mice had lower glucose than vehicle (p < 0.05) and HF group had higher glucose than LF group (p < 0.01). HOMA-IR scores at sacrifice significantly differed (p < 0.05); chemotherapy mice had lower scores than vehicle  (p < 0.05) and mice on the LF and HF n-3 diets had lower scores than the HF diet (p < 0.01; p < 0.05 respectively). Conclusions Chemotherapy lowered body weight and body fat in mice, potentially contributing to decreases in blood glucose and insulin resistance. EPA + DHA enrichment of a HF diet reduced insulin resistance in mice comparable to a LF diet group. This occurred in both chemotherapy and vehicle treated mice, despite LF diet-fed mice having lower body weight and adiposity. Underlying mechanisms are being investigated. Funding Sources NIH #5R01CA18994.

Different Responses to a High-Fat Diet in IL-6 Conditional Knockout Mice Driven by Constitutive GFAP-Cre and Synapsin 1-Cre Expression

2019 ◽  
Vol 109 (2) ◽  
pp. 113-130 ◽  
Author(s):  
Olaya Fernández-Gayol ◽  
Paula Sanchis ◽  
Kevin Aguilar ◽  
Alicia Navarro-Sempere ◽  
Gemma Comes ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Control Diet ◽  
Conditional Knockout ◽  
Mrna Levels ◽  
High Fat ◽  
Significant Difference ◽  
Cellular Source ◽  
The Central Nervous System ◽  
Synapsin 1

Background/Aims: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, at least in part through actions in the central nervous system (CNS) from local sources. Methods: We herewith report results obtained in conditional IL-6 KO mice for brain cells (Il6ΔGfap and Il6ΔSyn). Results: The reporter RiboTag mouse line demonstrated specific astrocytic expression of GFAP-dependent Cre in the hypothalamus but not in other brain areas, whereas that of synapsin 1-dependent Cre was specific for neurons. Feeding a high-fat diet (HFD) or a control diet showed that Il6ΔGfap and Il6ΔSyn mice were more prone and resistant, respectively, to HFD-induced obesity. Energy intake was not altered in HFD experiments, but it was reduced in Il6ΔSyn male mice following a 24-h fast. HFD increased circulating insulin, leptin, and cholesterol levels, decreased triglycerides, and caused impaired responses to the insulin and glucose tolerance tests. In Il6ΔGfap mice, the only significant difference observed was an increase in insulin levels of females, whereas in Il6ΔSyn mice the effects of HFD were decreased. Hypothalamic Agrp expression was significantly decreased by HFD, further decreased in Il6ΔGfap, and increased in Il6ΔSyn female mice. Hypothalamic Il-6 mRNA levels were not decreased in Il6ΔSyn mice and even increased in Il6ΔGfapmale mice. Microarray analysis of hypothalamic RNA showed that female Il6ΔGfap mice had increased interferon-related pathways and affected processes in behavior, modulation of chemical synaptic transmission, learning, and memory. Conclusion: The present results demonstrate that brain production of IL-6 regulates body weight in the context of caloric excess and that the cellular source is critical.

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