Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats

AbstractPrevious studies indicate that the administration of melatonin caused body weight and abdominal visceral fat reductions in rodent models of hyperadiposity. The objective of the present study performed in high-fat fed rats was to evaluate the activity of melatonin on gene expression of some medial basal hypothalamus (MBH) signals involved in feeding behavior regulation, including neuropeptide Y (NPY), proopiomelanocortin (POMC), prolactin-releasing peptide (PrRP), leptin- and insulin-receptors (R) and insulin-R substrate (IRS)-1 and -2. Blood levels of leptin and adiponectin were also measured.Adult Wistar male rats were divided into four groups (n=16 per group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet+melatonin; (iv) control diet+melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions: (a) tap water; (b) 25 μg/mL of melatonin.After 10 weeks, the high-fat fed rats showed augmented MBH mRNA levels of NPY, leptin-R, PrRP, insulin-R, IRS-1 and IRS-2. The concomitant administration of melatonin counteracted this increase. Feeding of rats with a high-fat diet augmented expression of the MBH POMC gene through an effect insensitive to melatonin treatment. The augmented levels of circulating leptin and adiponectin seen in high-fat fed rats were counteracted by melatonin as was the augmented body weight: melatonin significantly attenuated a body weight increase in high-fat fed rats without affecting chow or water consumption. Melatonin augmented plasma leptin and adiponectin in control rats.The results indicate that an effect on gene expression of feeding behavior signals at the central nervous system (CNS) may complement a peripheral rise of the energy expenditure produced by melatonin to decrease body weight in high-fat fed rats.

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

Neuroendocrinology ◽

10.1159/000496845 ◽

2019 ◽

Vol 109 (2) ◽

pp. 113-130 ◽

Cited By ~ 9

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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Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

Journal of Endocrinology ◽

10.1530/joe-13-0526 ◽

2014 ◽

Vol 221 (3) ◽

pp. 381-390 ◽

Cited By ~ 21

Author(s):

Gustavo W Fernandes ◽

Cintia B Ueta ◽

Tatiane L Fonseca ◽

Cecilia H A Gouveia ◽

Carmen L Lancellotti ◽

...

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Liver Steatosis ◽

Mrna Levels ◽

High Fat ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

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

Physiological Genomics ◽

10.1152/physiolgenomics.00032.2016 ◽

2016 ◽

Vol 48 (7) ◽

pp. 491-501 ◽

Cited By ~ 9

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.

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Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽

10.1161/circ.118.suppl_18.s_1169-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Rieko Takanabe ◽

Koh Ono ◽

Tomohide Takaya ◽

Takahiro Horie ◽

Hiromichi Wada ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

High Fat Diet ◽

Control Cell ◽

High Fat ◽

Expression Levels ◽

Mesenteric Fat ◽

Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

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Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α

British Journal Of Nutrition ◽

10.1017/s0007114507207627 ◽

2007 ◽

Vol 97 (2) ◽

pp. 389-398 ◽

Cited By ~ 131

Author(s):

Patricia Pérez-Matute ◽

Nerea Pérez-Echarri ◽

J. Alfredo Martínez ◽

Amelia Marti ◽

María J. Moreno-Aliaga

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Body Weight Gain ◽

Control Diet ◽

Cafeteria Diet ◽

High Fat ◽

Beneficial Effects

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0·09), a decrease in food intake (P < 0·01) and an increase in leptin production (P < 0·05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0·05) which could be secondary to the inhibition of the adipogenic transcription factor PPARγ gene expression (P < 0·001), and also to the increase in apoptosis (P < 0·05) found in rats fed with a control diet. TNFα gene expression was significantly increased (P < 0·05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0·01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFα and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

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Effects of a Mixed Limosilactobacillus fermentum Formulation with Claimed Probiotic Properties on Cardiometabolic Variables, Biomarkers of Inflammation and Oxidative Stress in Male Rats Fed a High-Fat Diet

Foods ◽

10.3390/foods10092202 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2202

Author(s):

Micaelle Oliveira de Luna Freire ◽

Luciana Caroline Paulino do Nascimento ◽

Kataryne Árabe Rimá de Oliveira ◽

Alisson Macário de Oliveira ◽

Thiago Henrique Napoleão ◽

...

Keyword(s):

Oxidative Stress ◽

High Fat Diet ◽

Control Diet ◽

Male Rats ◽

Control Group ◽

Low Grade ◽

Probiotic Properties ◽

High Fat ◽

Low Grade Inflammation ◽

And Oxidative Stress

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.

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

npj Science of Food ◽

10.1038/s41538-019-0050-z ◽

2019 ◽

Vol 3 (1) ◽

Cited By ~ 2

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.

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SO023HEPATOCYTE GROWTH FACTOR (HGF) PRECLUDE HIGH-FAT DIET-INDUCED OBESITY AND IMPROVED INSULIN RESISTANCE IN MICE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so023 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Jun Muratsu ◽

Yoshiaki Taniyama ◽

Fumihiro Sanada ◽

Atsuyuki Morishima ◽

Katsuhiko Sakaguchi ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

Growth Factor ◽

Inflammatory Mediators ◽

High Fat Diet ◽

Neutralizing Antibody ◽

Mrna Levels ◽

Wild Type ◽

High Fat

Abstract Background and Aims Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. Method In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4-5 times higher serum HGF levels than wild-type mice were used. We chose cardiac specific HGF overexpression, as other strain of HGF transgenic mice such as liver and kidney specific HGF overexpression mice develop cancer and cystic diseases, which are rare in the heart. In the present study, using HGF-Tg mice and anti-HGF neutralizing antibody (HGF-Ab), we explored the role of HGF in obese and insulin resistance induced by high fat diet (HFD) for 14 weeks (200 or 400ug/week). Results With normal chow diet (ND), there were no significant changes in body weight between WT and HGF-Tg mice. While body weight in wild-type mice fed with HFD for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. Insulin resistance in obesity arises from the combination of altered functions of insulin target cells (e.g., liver, skeletal muscle, and adipose tissue) and the accumulation of macrophages that secrete pro-inflammatory mediators in adipose tissue. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. In the gWAT, the mRNA levels of the mature macrophage marker F4/80, the chemoattractants, MCP-1 and CXCL2, and the inflammatory cytokines, such as TNF-α and iNOS, were significantly increased in WT mice fed with HFD. However, these levels were markedly reduced in HGF-Tg mice fed with HFD. Additionally, activation of Akt by insulin administration was significantly reduced in the gWAT SM, and liver by HFD; however, this activation was restored in HGF-Tg mice. Moreover, insulin-induced Akt signaling was decreased in HGF-Ab groups as compared to saline group under HFD condition. Importantly, HFD significantly increased the level of HGF mRNA by approximately 2 fold in gWAT, SM, and liver without changing cMet expression. All together, these data indicate that the HGF as one of the systemic gWAT, SM, and liver-derived growth factor plays a role in compensatory mechanism against insulin-resistance through the at least anti-inflammatory effect in adipose tissue. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. Conclusion HGF suppresses inflammation in adipose tissue induced by a high-fat diet, and as a result improves systemic insulin resistance. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.

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Lactobacillus Rhamnosus Yoba Modulates Serum Cholesterol in Normo-Lipidemic Wistar Rats Fed a High Fat Diet (P20-013-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz040.p20-013-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Adaku Iwueke ◽

Conrad Miruka ◽

John Ejekwumadu ◽

Ronald Kiiza ◽

Pius Theophilus

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Wistar Rats ◽

Ldl Cholesterol ◽

Lactobacillus Rhamnosus ◽

Hdl Cholesterol ◽

Male Rats ◽

Fermented Foods ◽

Distilled Water ◽

High Fat

Abstract Objectives The study was aimed at assessing the effects of Lactobacillus rhamnosus yoba on the serum lipid profile and body weight of male Wistar rats fed a high fat diet. Methods 20 seven week old male rats weighing between 120 g and 180 g were used for the study and divided into 4 groups of 5 rats each. The control group was fed normal mice pellets and distilled water, while the other groups were fed mice pellets supplemented with 3% cholesterol and 2% saturated fat in addition to any of distilled water, Lactobacillus rhamnosus yoba or Norvastatin respectively. The body weight was measured at the start of the study and after 2 weeks while serum parameters were measured after 8 weeks. Data was analyzed using SPSS Version 20. ANOVA and Tukey's tests determined significant differences in means at 95% confidence interval. Results Lactobacillus rhamnosus yoba significantly (P < 0.005) modulated weight gain, serum total cholesterol and triglycerides when compared to the control. Similarly, LDL-cholesterol was significantly modulated (P < 0.005) while HDL-cholesterol was significantly enhanced (P < 0.005) when compared to the control. Conclusions The ability of Lactobacillus rhamnosus yoba to elevate HDL cholesterol and modulate LDL-cholesterol without the side effects of statins makes it a potential functional food. In line with the findings, the present study justifies the use of Lactobacillus rhamnosus yoba as a probiotic in fermented foods. Funding Sources NA.

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