scholarly journals Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongxiao Zhang ◽  
Satoshi Yamaguchi ◽  
Xinhao Zhang ◽  
Boxuan Yang ◽  
Naoko Kurooka ◽  
...  
Keyword(s):  
Food Intake ◽  
Target Gene ◽  
Potential Candidate ◽  
Appetite Control ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Hypothalamic Arcuate Nucleus ◽  
High Sucrose ◽  
Major Target

In obesity and type 2 diabetes, numerous genes are differentially expressed, and microRNAs are involved in transcriptional regulation of target mRNAs, but miRNAs critically involved in the appetite control are not known. Here, we identified upregulation of miR-342-3p and its host gene Evl in brain and adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir342 (-/-) mice fed with HFHS chow were protected from obesity and diabetes. The hypothalamic arcuate nucleus neurons co-express Mir342 and EVL. The percentage of activated NPY+pSTAT3+ neurons were reduced, while POMC+pSTAT3+ neurons increased in Mir342 (-/-) mice, and they demonstrated the reduction of food intake and amelioration of metabolic phenotypes. Snap25 was identified as a major target gene of miR-342-3p and the reduced expression of Snap25 may link to functional impairment hypothalamic neurons and excess of food intake. The inhibition of miR-342-3p may be a potential candidate for miRNA-based therapy.

scholarly journals High-Fat Diet and Age-Dependent Effects of IgA-Bearing Cell Populations in the Small Intestinal Lamina Propria in Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1165
Author(s):  
Yuta Sakamoto ◽  
Masatoshi Niwa ◽  
Ken Muramatsu ◽  
Satoshi Shimo
Keyword(s):  
Immune Function ◽  
Lamina Propria ◽  
High Fat Diet ◽  
Immunoglobulin A ◽  
Immune Functions ◽  
High Fat ◽  
Intestinal Villi ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

Several studies highlighted that obesity and diabetes reduce immune function. However, changes in the distribution of immunoglobins (Igs), including immunoglobulin-A (IgA), that have an important function in mucosal immunity in the intestinal tract, are unclear. This study aimed to investigate the impaired immune functions in the context of a diet-induced obese murine model via the assessment of the Igs in the intestinal villi. We used mice fed a high-fat diet (HFD) from four to 12 or 20 weeks of age. The distributions of IgA, IgM, and IgG1 were observed by immunohistochemistry. Interestingly, we observed that IgA was immunolocalized in many cells of the lamina propria and that immunopositive cells increased in mice aged 12 to 20 weeks. Notably, mice fed HFD showed a reduced number of IgA-immunopositive cells in the intestinal villi compared to those fed standard chow. Of note, the levels of IgM and IgG1 were also reduced in HFD fed mice. These results provide insights into the impaired mucosal immune function arising from diet-induced obesity and type 2 diabetes.

LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice

2002 ◽  
Vol 282 (1) ◽  
pp. E207-E214 ◽  
Author(s):  
Sandra A. Schreyer ◽  
Cynthia Vick ◽  
Theodore C. Lystig ◽  
Paul Mystkowski ◽  
Renée C. LeBoeuf
Keyword(s):  
Apolipoprotein E ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Wild Type ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Glucose And Lipid Homeostasis

The aim of this study was to determine whether phenotypes associated with type 2 diabetes are altered in dyslipidemic obese mice. C57BL/6 wild-type, low-density lipoprotein (LDL) receptor-deficient (LDLR−/−), and apolipoprotein E-deficient (apoE−/−) mice were fed a high-fat, high-carbohydrate diet (diabetogenic diet), and the development of obesity, diabetes, and hypertriglyceridemia was examined. Wild-type mice became obese and developed hyperglycemia, but not hypertriglyceridemia, in response to this diet. LDLR−/− mice fed the diabetogenic diet became more obese than wild-type mice and developed severe hypertriglyceridemia and hyperleptinemia. Surprisingly, glucose levels were only modestly higher and insulin levels and insulin-to-glucose ratios were not strikingly different from those of wild-type mice. In contrast, diabetogenic diet-fed apoE−/− mice were resistant to changes in glucose and lipid homeostasis despite becoming obese. These data suggest that modifications in lipoprotein profiles associated with loss of the LDL receptor or apoE function have profound and unique consequences on susceptibility to diet-induced obesity and type 2 diabetic phenotypes.

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 Kidney osteoclast factors and matrix metalloproteinase expression in a mice model of diet-induced obesity and diabetes

2019 ◽  
Author(s):  
Francine dos Santos-Macedo ◽  
Bianca Martins-Gregorio ◽  
Elan Cardozo Paes-de-Almeida ◽  
Leonardo de Souza Mendonça ◽  
Rebeca de Souza Azevedo ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Renal Tissue ◽  
Inflammatory Cell Infiltrate ◽  
Mice Model ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
Underlying Mechanisms ◽  
Mononuclear Inflammatory Cell ◽  
High Sucrose

ABSTRACTThe role of RANKL/RANK/OPG system on bone remodeling is well known, and there is evidence that it is also important to cardiovascular and kidney pathology, although the underlying mechanisms are not elucidated so far. Thus, we investigated in a mice model of diet-induced obesity and diabetes if renal histopathological changes are associated with the expression of RANKL/RANK/OPG system and matrix metalloproteinases (MMPs). Three months old C57BL/6 mice were fed with control (AIN93M) or high-fat high sucrose (HFHS) diets for 21 weeks (CEUA/UFF #647/15). The HFHS group showed weight gain (+35%, P=0.0001), increased epididymal, inguinal and retroperitoneal fat pad weight (+121 %, P = 0.0006; +287 %, P = 0.0007 and; +286 %, P < 0.0001, respectively), and hyperglycemia (+43%, P=0.02). The kidney of some HFHS fed mice displayed mononuclear inflammatory cell infiltrate (40%), perivascular fibrosis (20%), and focal tubule mineralization (20%). Glomeruli hypertrophy was not detected. Unexpectedly, OPG, RANK, MMP-2 and MMP-9 expression was not altered in HFHS groups (Western blot analysis). In conclusion, the expression of RANKL/RANK/OPG system proteins and MMPs was not influenced by diet-induced obesity and diabetes in the kidney of male C57BL/6 mice, although some adverse histopathological remodeling is noticed in the renal tissue.

scholarly journals Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2932
Author(s):  
Marion Régnier ◽  
Marialetizia Rastelli ◽  
Arianne Morissette ◽  
Francesco Suriano ◽  
Tiphaine Le Roy ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Strongly Correlated ◽  
Akkermansia Muciniphila ◽  
Diet Induced Obesity ◽  
Triglyceride Accumulation ◽  
Obesity And Diabetes ◽  
Nutritional Compounds ◽  
Improve Health

Obesity and obesity-related disorders, such as type 2 diabetes have been progressively increasing worldwide and treatments have failed to counteract their progression. Growing evidence have demonstrated that gut microbiota is associated with the incidence of these pathologies. Hence, the identification of new nutritional compounds, able to improve health through a modulation of gut microbiota, is gaining interest. In this context, the aim of this study was to investigate the gut-driving effects of rhubarb extract in a context of diet-induced obesity and diabetes. Eight weeks old C57BL6/J male mice were fed a control diet (CTRL), a high fat and high sucrose diet (HFHS) or a HFHS diet supplemented with 0.3% (g/g) of rhubarb extract for eight weeks. Rhubarb supplementation fully prevented HFHS-induced obesity, diabetes, visceral adiposity, adipose tissue inflammation and liver triglyceride accumulation, without any modification in food intake. By combining sequencing and qPCR methods, we found that all these effects were associated with a blooming of Akkermansia muciniphila, which is strongly correlated with increased expression of Reg3γ in the colon. Our data showed that rhubarb supplementation is sufficient to protect against metabolic disorders induced by a diet rich in lipid and carbohydrates in association with a reciprocal interaction between Akkermansia muciniphila and Reg3γ.

scholarly journals Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation

2015 ◽  
Vol 226 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Farhana Naznin ◽  
Koji Toshinai ◽  
T M Zaved Waise ◽  
Cherl NamKoong ◽  
Abu Saleh Md Moin ◽  
...  
Keyword(s):  
Food Intake ◽  
Inflammatory Responses ◽  
Nodose Ganglion ◽  
Afferent Nerve ◽  
Ghrelin Receptor ◽  
Diet Induced Obesity ◽  
Orexigenic Peptide ◽  
Hypothalamic Arcuate Nucleus ◽  
Vagal Afferent ◽  
Amp Activated Protein Kinase

Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway. Administration (s.c.) of ghrelin did not induce food intake, suppression of oxygen consumption, electrical activity of the vagal afferent nerve, phosphorylation of ERK2 and AMP-activated protein kinase alpha in the nodose ganglion, or Fos expression in hypothalamic arcuate nucleus of mice fed a HFD for 12 weeks. Administration of anti-ghrelin IgG did not induce suppression of food intake in HFD-fed mice. Expression levels of ghrelin receptor mRNA in the nodose ganglion and hypothalamus of HFD-fed mice were reduced. Inflammatory responses, including upregulation of macrophage/microglia markers and inflammatory cytokines, occurred in the nodose ganglion and hypothalamus of HFD-fed mice. A HFD blunted ghrelin signaling in the nodose ganglion via a mechanism involvingin situactivation of inflammation. These results indicate that ghrelin resistance in the obese state may be caused by dysregulation of ghrelin signaling via the vagal afferent.

scholarly journals Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet

2015 ◽  
Vol 228 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Tetsuya Kouno ◽  
Nobuteru Akiyama ◽  
Takahito Ito ◽  
Tomohiko Okuda ◽  
Isamu Nanchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Acylated Ghrelin ◽  
High Fat ◽  
Obesity And Diabetes ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose

Ghrelin is an appetite-stimulating hormone secreted from stomach. Since the discovery that acylation of the serine-3 residue by ghrelin O-acyltransferase (GOAT) is essential for exerting its functions, GOAT has been regarded as an therapeutic target for attenuating appetite, and thus for the treatment of obesity and diabetes. However, contrary to the expectations, GOAT-knockout (KO) mice have not shown meaningful body weight reduction, under high-fat diet. Here, in this study, we sought to determine whether GOAT has a role in body weight regulation and glucose metabolism with a focus on dietary sucrose, because macronutrient composition of diet is important for appetite regulation. We found that peripherally administered acylated-ghrelin, but not unacylated one, stimulated sucrose consumption in a two-bottle-drinking test. The role of acylated-ghrelin in sucrose preference was further supported by the finding that GOAT KO mice consumed less sucrose solution compared with WT littermates. Then, we investigated the effect of dietary composition of sucrose on food intake and body weight in GOAT KO and WT mice. As a result, when fed on high-fat diet, food intake and body weight were similar between GOAT KO and WT mice. However, when fed on high-fat, high-sucrose diet, GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, leading to amelioration of glucose metabolism. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity and metabolic disorders caused by overeating of palatable food.

scholarly journals Validation of reference genes for RT-qPCR in cardiac tissue of rats induced to obesity and diabetes

2020 ◽  
Vol 9 (11) ◽  
pp. e1599119702
Author(s):  
Marina Martins de Oliveira ◽  
Kalynka Gabriella do Livramento ◽  
Maísa Lamounier Magalhães ◽  
Luciano Vilela Paiva ◽  
Ana Paula Peconick
Keyword(s):  
Gene Expression ◽  
Reference Genes ◽  
Target Gene ◽  
Target Genes ◽  
Cardiac Tissue ◽  
Rna Extraction ◽  
Obesity And Diabetes ◽  
The Stability ◽  
Universal Reference

The validation of reference genes is an essential step for any RT-qPCR analysis. In this way, the present paper aimed to identify and validate reference genes for RT-qPCR in cardiac tissue of rats of the Rattus norvegicus albinus specie, submitted to obesity associated or not to type 2 diabetes mellitus. For this, the metabolic changes were induced at the 42nd day of life and the euthanasia was performed on the 70th day. The heart apexes were collected and destinates for RNA extraction. The RT-qPCR technique was performed in own thermocycler, the efficiency of the primers found by the LinReg software and the stability of the expression of the reference genes in the samples was analyzed by the RefFinder algorithm. The candidates for reference genes were GAPDH, POLR2A, RPL32, and RPL4 and the target gene used to verify the differences in gene expression of candidates for reference genes was CMA1. The obese animals showed a decrease in CMA1 gene expression when compared to the two most stable reference genes. The opposite occurs when it is compared to the two less stable reference genes. The GAPDH and POLR2A genes are the best to normalize the reactions with the samples in question. There is no universal reference gene for all situations, which requires systematic validation for each situation. The use of unvalidated reference genes may compromise the interpretation of the expression of the target genes, which would prevent the reflection of the actual situation.

scholarly journals Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc1l1−/− mice

2008 ◽  
Vol 295 (4) ◽  
pp. G776-G783 ◽  
Author(s):  
Eric D. Labonté ◽  
Lisa M. Camarota ◽  
Juan C. Rojas ◽  
Ronald J. Jandacek ◽  
Dean E. Gilham ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Weight Gain ◽  
Saturated Fatty Acids ◽  
Cholesterol Absorption ◽  
Fatty Acid Transport ◽  
Long Chain Fatty Acids ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes ◽  
The Impact ◽  
High Sucrose

The impact of NPC1L1 and ezetimibe on cholesterol absorption are well documented. However, their potential consequences relative to absorption and metabolism of other nutrients have been only minimally investigated. Thus studies were undertaken to investigate the possible effects of this protein and drug on fat absorption, weight gain, and glucose metabolism by using Npc1l1−/− and ezetimibe-treated mice fed control and high-fat, high-sucrose diets. Results show that lack of NPC1L1 or treatment with ezetimibe reduces weight gain when animals are fed a diabetogenic diet. This resistance to diet-induced obesity results, at least in part, from significantly reduced absorption of dietary saturated fatty acids, particularly stearate and palmitate, since food intake did not differ between groups. Expression analysis showed less fatty acid transport protein 4 (FATP4) in intestinal scrapings of Npc1l1−/− and ezetimibe-treated mice, suggesting an important role for FATP4 in intestinal absorption of long-chain fatty acids. Concomitant with resistance to weight gain, lack of NPC1L1 or treatment with ezetimibe also conferred protection against diet-induced hyperglycemia and insulin resistance. These unexpected beneficial results may be clinically important, given the focus on NPC1L1 as a target for the treatment of hypercholesterolemia.

scholarly journals Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4

2022 ◽  
Vol 12 ◽  
Author(s):  
Satoshi Yamaguchi ◽  
Dongxiao Zhang ◽  
Akihiro Katayama ◽  
Naoko Kurooka ◽  
Ryosuke Sugawara ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Potential Candidate ◽  
High Fat ◽  
S6 Kinase ◽  
Diet Induced Obesity ◽  
Ribosomal Protein S6 ◽  
The Common ◽  
Direct Target ◽  
Kinase Pathway ◽  
High Sucrose

MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222flox/y. Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy.

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