scholarly journals Perturbation of Hypothalamic MicroRNA Expression Patterns in Male Rats After Metabolic Distress: Impact of Obesity and Conditions of Negative Energy Balance

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1838-1850 ◽  
Author(s):  
Susana Sangiao-Alvarellos ◽  
Lara Pena-Bello ◽  
María Manfredi-Lozano ◽  
Manuel Tena-Sempere ◽  
Fernando Cordido

The hypothalamus plays a crucial role in body weight homeostasis through an intricate network of neuronal circuits that are under the precise regulation of peripheral hormones and central transmitters. Although deregulated function of such circuits might be a major contributing factor in obesity, the molecular mechanisms responsible for the hypothalamic control of energy balance remain partially unknown. MicroRNAs (miRNAs) have been recognized as key regulators of different biological processes, including insulin sensitivity and glucose metabolism. However, the roles of miRNA pathways in the control of metabolism have been mostly addressed in peripheral tissues, whereas the potential deregulation of miRNA expression in the hypothalamus in conditions of metabolic distress remains as yet unexplored. In this work, we used high-throughput screening to define to what extent the hypothalamic profiles of miRNA expression are perturbed in two extreme conditions of nutritional stress in male rats, namely chronic caloric restriction and high-fat diet–induced obesity. Our analyses allowed the identification of sets of miRNAs, including let-7a, mir-9*, mir-30e, mir-132, mir-145, mir-200a, and mir-218, whose expression patterns in the hypothalamus were jointly altered by caloric restriction and/or a high-fat diet. The predicted targets of these miRNAs include several elements of key inflammatory and metabolic pathways, including insulin and leptin. Our study is the first to disclose the impact of nutritional challenges on the hypothalamic miRNA expression profiles. These data will help to characterize the molecular miRNA signature of the hypothalamus in extreme metabolic conditions and pave the way for targeted mechanistic analyses of the involvement of deregulated central miRNAs pathways in the pathogenesis of obesity and related disorders.

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.


2021 ◽  
Vol 91 ◽  
pp. 108598
Author(s):  
Diego Hernández-Saavedra ◽  
Laura Moody ◽  
Xinyu Tang ◽  
Zachary J. Goldberg ◽  
Alex P. Wang ◽  
...  

2018 ◽  
Vol 315 (6) ◽  
pp. H1713-H1723 ◽  
Author(s):  
Lia E. Taylor ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Babak Baban ◽  
Jennifer C. Sullivan

Evidence supports a sex difference in the impact of a high-fat diet (HFD) on cardiovascular outcomes, with male experimental animals exhibiting greater increases in blood pressure (BP) than female experimental animals. The immune system has been implicated in HFD-induced increases in BP, and there is a sex difference in T-cell activation in hypertension. The goal of this study was to determine the impact of HFD on BP and aortic and renal T cell profiles in male and female Dahl salt-sensitive (DSS) rats. We hypothesized that male DSS rats would have greater increases in BP and T cell infiltration in response to a HFD compared with female DSS rats. BP was measured by tail-cuff plethysmography, and aortic and renal T cells were assessed by flow cytometric analysis in male and female DSS rats on a normal-fat diet (NFD) or HFD from 12 to 16 wk of age. Four weeks of HFD increased BP in male and female DSS rats to a similar degree. Increases in BP were accompanied by increased percentages of CD4+ T cells and T helper (Th)17 cells in both sexes, although male rats had more proinflammatory T cells. Percentages of renal CD3+ and CD4+ T cells as well as Th17 cells were increased in both sexes by the HFD, although the increase in CD3+ T cells was greater in male rats. HFD also decreased the percentage of aortic and renal regulatory T cells in both sexes, although female rats maintained more regulatory T cells than male rats regardless of diet. In conclusion, both male and female DSS rats exhibit BP sensitivity to a HFD; however, the mechanisms mediating HFD-induced increases in BP may be distinct as male rats exhibit greater increases in the percentage of proinflammatory T cells than female rats. NEW & NOTEWORTHY Our study demonstrates that male and female Dahl salt-sensitive rats exhibit similar increases in blood pressure to a high-fat diet and an increase in aortic and renal T cells. These results are in contrast to studies showing that female rats remain normotensive and/or upregulate regulatory T cells in response to hypertensive stimuli compared with male rats. Our data suggest that a 4-wk high-fat diet has sex-specific effects on the T cell profile in Dahl salt-sensitive rats.


Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 843-850 ◽  
Author(s):  
Yuxiang Sun ◽  
Nancy F. Butte ◽  
Jose M. Garcia ◽  
Roy G. Smith

Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R), are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin−/− and Ghsr−/− mice under conditions of both positive (high-fat diet) and negative (caloric restriction) energy balance. In contrast to results from young N2 mutant mice, changes in body weight and energy expenditure are not clearly distinguishable across genotypes. Although respiratory quotient was lower in mice fed a high-fat diet, no differences were evident between littermate wild-type and null genotypes. With normal chow, a modest decrease trend in respiratory quotient was detected in ghrelin−/− mice but not in Ghsr−/− mice. Under caloric restriction, the weight loss of ghrelin−/− and Ghsr−/− mice was identical to wild-type littermates, but blood glucose levels were significantly lower. We conclude that adult congenic ghrelin−/− and Ghsr−/− mice are not resistant to diet-induced obesity but under conditions of negative energy balance show impairment in maintaining glucose homeostasis. These results support our hypothesis that the primary metabolic function of ghrelin in adult mice is to modulate glucose sensing and insulin sensitivity, rather than directly regulate energy intake and energy expenditure.


2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Maoxing Pan ◽  
Yuanjun Deng ◽  
Chuiyang Zheng ◽  
Huan Nie ◽  
Kairui Tang ◽  
...  

Objective. The purpose of present study was to investigate the potential mechanism underlying the protective effect of Shenling Baizhu San (SLBZS) on nonalcoholic fatty liver disease (NAFLD) by microRNA (miRNA) sequencing. Methods. Thirty male Wistar rats were randomly divided into a normal control (NC) group, a high-fat diet (HFD) group, and an SLBZS group. After 12 weeks, the biochemical parameters and liver histologies of the rats were assessed. The Illumina HiSeq 2500 sequencing platform was used to analyse the hepatic miRNA expression profiles. Representative differentially expressed miRNAs were further validated by qRT-PCR. The functions of the differentially expressed miRNAs were analysed by bioinformatics. Results. Our results identified 102 miRNAs that were differentially expressed in the HFD group compared with the NC group. Among those differentially expressed miRNAs, the expression levels of 28 miRNAs were reversed by SLBZS administration, suggesting the modulation effect of SLBZS on hepatic miRNA expression profiles. The qRT-PCR results confirmed that the expression levels of miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p were consistent with those detected by sequencing. Bioinformatics analyses indicated that the target genes of the differentially expressed miRNAs reversed by SLBZS were mainly related to metabolic pathways. Conclusion. This study provides novel insights into the mechanism of SLBZS in protecting against NAFLD; this mechanism may be partly related to the modulation of hepatic miRNA expression and their target pathways.


2019 ◽  
Author(s):  
Yuqing Wu ◽  
Yue Guan ◽  
Fan Ling ◽  
Qiushuang Zhu ◽  
Dandan Zhang ◽  
...  

Abstract Background: A High-fat diet has been reported to produce excess lipid accumulation and increase inflammatory factors and oxidative stress in various metabolic diseases. Caloric restriction (CR) is one of the most valuable tools in reducing inflammation, enhancing anti-oxidative activity and ameliorating various metabolic diseases. However, excess CR may restrain growth, development and normal physiological processes. Our study was conducted to investigate the effects of a high-fat diet containing the same number of calories as a basic diet on the health and gene expression patterns of rats.Methods: 30 Wistar male rats were randomly devided into a normal control (NC) group, an equicaloric high-fat (EHF) group as the NC group, and a high-fat (HF) ad libitum group. Food consumption and body weight were recorded once a week. Blood biochemistical and genomic assessments of the liver were carried out after intervention for 20 weeks. Results: Compared with the NC group, serum triglycerides (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST) and andalanine aminotransferase (ALT) levels were significantly increased in the HF group, and the serum levels of interleukin- 6 (IL-6), reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased in the HF group. Compared with the HF group, serum TG,TCHO,LDL-C, AST, ALT, IL-6, ROS levels were significantly decreased in the EHF group, and the serum levels of GSH and superoxide dismutase (SOD) were also significantly increased. Histological studies showed decreased macrovesicular steatosis, inflammatory cell infiltration and structural damagein EHF group compared to the HF group. In addition, transcription analysis revealed that an EHF led tochanges in gene expression, including a reduction inToll-like receptor 4 (TRL4),which inhibited NF-kappa B signaling pathway and upregulatedglutathione S-transterases (GSTs) to increase antiocidative activity.Conclusions: an EHF restored deleterious changes in the health and gene expression patterns induced by a high-fat diet ad libitum in rats via reduced inflammation and increased antioxidative activity.


2020 ◽  
Vol 318 (3) ◽  
pp. R515-R528 ◽  
Author(s):  
Tiffany Y. Yang ◽  
Jennie C. Gardner ◽  
Zijun Gao ◽  
Yuan-Xiang Pan ◽  
Nu-Chu Liang

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period. Exercise is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates glucocorticoid (GC) release, which can alter dietary preferences. Here, we examined the role of the HPA axis and GC signaling in mediating exercise-induced changes in diet preference and the associated neurobiological adaptations that may underlie sex differences in diet choice patterns. Experiment 1 revealed that adrenalectomy did not significantly alter the initiation and persistence of running-induced HF diet avoidance in male rats. Experiment 2 showed that acute WR resulted in greater neural activation than chronic WR in the medial prefrontal (mPFC) and insular cortices (IC) in male rats. Experiment 3 revealed sex differences in the molecular adaptation to exercise and diet preference. First, exercise increased gene expression of fkbp5 in the mPFC, IC, and hippocampus of WR females but had limited influence in males. Second, male and female WR rats that reversed or maintained HF diet avoidance showed distinct sex- and HF diet preference-dependent expression profiles of genes involved in cortical GC signaling (e.g., nr3c1, nr3c2, and src1). Taken together, our results suggest sex differences in region-specific neural adaptations may underlie sex differences in diet preference and the health benefits from exercise.


2021 ◽  
Author(s):  
Qiao Jie ◽  
Yue-Zhong Ren ◽  
Yi-wen Wu

High-fat diets(HFD)are defined as lipids accounting for exceeded 30% of total energy in-take, and current research is mostly 45% and 60%. With a view of the tendency that patients who...


Sign in / Sign up

Export Citation Format

Share Document