Short-term but not long-term high-fat diet induces an increase in gene expression of gonadotropic hormones and GPR120 in the male mouse pituitary gland

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.

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Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0885-9872 ◽

2019 ◽

Vol 128 (01) ◽

pp. 30-37

Author(s):

Luciele Guerra Minuzzi ◽

Gabriel Keine Kuga ◽

Leonardo Breda ◽

Rafael Calais Gaspar ◽

Vitor Rosetto Muñoz ◽

...

Keyword(s):

Insulin Sensitivity ◽

Resistance Training ◽

High Fat Diet ◽

Calorie Intake ◽

Hepatic Tissue ◽

Chow Diet ◽

Adapter Protein ◽

High Fat ◽

Short Term

Abstract Background APPL1, an adapter protein, interact directly with adiponectin receptors mediating adiponectin signaling and acting as a critical regulator of the crosstalk between adiponectin and insulin signaling pathway. The inadequate level of physical activity, high-calorie intake, or both lead to adverse consequences on health, like insulin resistance. On the order hand, physical exercise acts positively in the insulin action. Purpose Here, we investigated the effects of short-term resistance training (RT) on APPL1 content and adiponectin pathway in the liver of mice fed a long-term high-fat diet. Methods Swiss mice were distributed into 3 groups: Mice that fed a chow diet (CTR); Mice fed a high-fat diet for 16 months (HFD); and mice fed a high-fat diet for 16 months and submitted to a climbing ladder exercise (RT) for 7 days (HFD-EXE). Results The results show that short-term RT increases the APPL1 content but wasn’t able to alter AdipoR1 and AdipoR2 content in the liver of HFD-EXE mice. However, this increase in the APPL1 content in response to RT was accompanied by improvement in the insulin sensitivity. Conclusion In summary, our data suggested that short-term RT improves glycemic homeostasis and increases APPL1 in the hepatic tissue of mice treated with long-term high-fat diet.

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Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00220.2015 ◽

2016 ◽

Vol 310 (7) ◽

pp. R640-R658 ◽

Cited By ~ 43

Author(s):

James E. Blevins ◽

Benjamin W. Thompson ◽

Vishwanath T. Anekonda ◽

Jacqueline M. Ho ◽

James L. Graham ◽

...

Keyword(s):

High Fat Diet ◽

High Fat ◽

Short Term ◽

Satiety Response ◽

Diet Induced Obesity ◽

Sustained Reduction ◽

Oxytocin Infusion ◽

Term Administration ◽

The Central Nervous System

Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.

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In Vivo Modulation of Mitochondrial Activity Determines HSC Engraftment and Post-Transplant Survival in Mice

Blood ◽

10.1182/blood.v120.21.213.213 ◽

2012 ◽

Vol 120 (21) ◽

pp. 213-213

Author(s):

Nicola Vannini ◽

Olaia M. Naveiras ◽

Vasco Campos ◽

Eija Pirinen ◽

Riekelt Houtkooper ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

High Fat Diet ◽

Mitochondrial Activity ◽

High Fat ◽

Short Term ◽

Hematopoietic Stem ◽

Post Transplant ◽

Progenitor Compartment

Abstract Abstract 213 Cellular metabolism is emerging as a potential fate determinant in cancer and stem cell biology, constituting a crucial regulator of the hematopoietic stem cell (HSC) pool [1–4]. The extremely low oxygen tension in the HSC microenvironment of the adult bone marrow forces HSCs into a low metabolic profile that is thought to enable their maintenance by protecting them from reactive oxygen species (ROS). Although HSC quiescence has for long been associated with low mitochondrial activity, as testified by the low rhodamine stain that marks primitive HSCs, we hypothesized that mitochondrial activation could be an HSC fate determinant in its own right. We thus set to investigate the implications of pharmacologically modulating mitochondrial activity during bone marrow transplantation, and have found that forcing mitochondrial activation in the post-transplant period dramatically increases survival. Specifically, we examined the mitochondrial content and activation profile of each murine hematopoietic stem and progenitor compartment. Long-term-HSCs (LT-HSC, Lin-cKit+Sca1+ (LKS) CD150+CD34-), short-term-HSCs (ST-HSC, LKS+150+34+), multipotent progenitors (MPPs, LKS+150-) and committed progenitors (PROG, Lin-cKit+Sca1-) display distinct mitochondrial profiles, with both mitochondrial content and activity increasing with differentiation. Indeed, we found that overall function of the hematopoietic progenitor and stem cell compartment can be resolved by mitochondrial activity alone, as illustrated by the fact that low mitochondrial activity LKS cells (TMRM low) can provide efficient long-term engraftment, while high mitochondrial activity LKS cells (TMRM high) cannot engraft in lethally irradiated mice. Moreover, low mitochondrial activity can equally predict efficiency of engraftment within the LT-HSC and ST-HSC compartments, opening the field to a novel method of discriminating a population of transitioning ST-HSCs that retain long-term engraftment capacity. Based on previous experience that a high-fat bone marrow microenvironment depletes short-term hematopoietic progenitors while conserving their long-term counterparts [5], we set to measure HSC mitochondrial activation in high-fat diet fed mice, known to decrease metabolic rate on a per cell basis through excess insulin/IGF-1 production. Congruently, we found lower mitochondrial activation as assessed by flow cytometry and RT-PCR analysis as well as a depletion of the short-term progenitor compartment in high fat versus control chow diet fed mice. We then tested the effects of a mitochondrial activator known to counteract the negative effects of high fat diet. We first analyzed the in vitro effect on HSC cell cycle kinetics, where no significant change in proliferation or division time was found. However, HSCs responded to the mitochondrial activator by increasing asynchrony, a behavior that is thought to directly correlate with asymmetric division [6]. As opposed to high-fat diet fed mice, mice fed with the mitochondrial activator showed an increase in ST-HSCs, while all the other hematopoietic compartments were comparable to mice fed on control diet. Given the dependency on short-term progenitors to rapidly reconstitute hematopoiesis following bone marrow transplantation, we tested the effect of pharmacological mitochondrial activation on the recovery of mice transplanted with a limiting HSC dose. Survival 3 weeks post-transplant was 80% in the treated group compared to 0% in the control group, as predicted by faster recovery of platelet and neutrophil counts. In conclusion, we have found that mitochondrial activation regulates the long-term to short-term HSC transition, unraveling mitochondrial modulation as a valuable drug target for post-transplant therapy. Identification of molecular pathways accountable for the metabolically mediated fate switch is currently ongoing. Disclosures: No relevant conflicts of interest to declare.

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Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model

Gene ◽

10.1016/j.gene.2004.06.015 ◽

2004 ◽

Vol 340 (1) ◽

pp. 99-109 ◽

Cited By ~ 172

Author(s):

Sujong Kim ◽

Insuk Sohn ◽

Joon-Ik Ahn ◽

Ki-Hwan Lee ◽

Yeon Sook Lee ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

High Fat Diet ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Hepatic Gene Expression ◽

High Fat ◽

Diet Induced Obesity

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Transcriptomic Alterations of the Aortic Intima and Media in Long-term High-fat Diet Fed Pigs and Its Reversal (P15-010-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz037.p15-010-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Dragan Milenkovic ◽

Agnieszka Gomułkiewicz ◽

Cecile Gladine ◽

Dariusz Janczak ◽

Irmina Grzegorek ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Expression Profile ◽

High Fat Diet ◽

Control Diet ◽

Cell Permeability ◽

High Fat ◽

Development Fund ◽

Cytoskeleton Organization

Abstract Objectives We have previously shown that 12 months (mo.) high-fat diet (HFD) in pigs led to pathophysiological alterations, incl. fattening and increased femoral artery intima-media-thickness, which were partly reversed after 3 mo. return to control diet (Zabek et al., PLoS One 2017). The aim of this study was to decipher underlying mechanism of action of these dietary interventions on the arteries by nutrigenomics analyses of intima and media of aorta. Methods 32 female pigs were divided into 3 groups: Control diet (CD) for 12 mo; HFD for 12 mo; 3) Reversal diet group (RD): HFD for 9 mo followed by CD for 3 mo After 12 mo animals were killed and abdominal aorta collected. RNA was isolated from aorta intima and media for whole genome microarray analyses followed by bioinformatics analyses. Results HFD compared to CD group significantly affected gene expression profile in intima with genes belonging to the chemotaxis, inflammation or endothelial permeability. RD induced gene expression profile was distinct from the CD group. This suggests that 3 mo of reversal to CD is not sufficient to correct gene expression changes induced by HFD. Comparison of RD profile with that of HFD group revealed a group of genes with opposite expression, e.g., genes regulating inflammation, toll-like cell signaling pathway or cytoskeleton organization involved in the regulation of cell permeability. This suggests that return to the RD only partly restored gene expression alterations due to the HFD. Significant changes in expression of genes in media following HFD were also observed, such as genes involved in cytoskeleton organization and migration MAPK signaling. As for intima, the expression profile of media of pigs on RD was different on that of these on CD diet. Compared to HFD, a group of genes involved in PI3K or MAPK pathways presented opposite expression suggesting that RD can partly correct the changes in genomic effect induced by HFD. Conclusions This study revealed genomic modifications induced by long-term HFD consumption on arterial intima and media. The return to normal diet for 3 mo was not sufficient to counteract the genomic effect of long-term HFD consumption. Funding Sources WROVASC Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund.

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Short-term high-fat diet primes excitatory synapses for long-term depression in orexin neurons

The Journal of Physiology ◽

10.1113/jp275177 ◽

2017 ◽

Vol 596 (2) ◽

pp. 305-316 ◽

Cited By ~ 10

Author(s):

Victoria Linehan ◽

Lisa Z. Fang ◽

Michiru Hirasawa

Keyword(s):

High Fat Diet ◽

Excitatory Synapses ◽

High Fat ◽

Short Term ◽

Long Term Depression

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Hepatic Gene Expression Profiling in Nrf2 Knockout Mice after Long-Term High-Fat Diet-Induced Obesity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/340731 ◽

2013 ◽

Vol 2013 ◽

pp. 1-17 ◽

Cited By ~ 11

Author(s):

Dionysios V. Chartoumpekis ◽

Panos G. Ziros ◽

Apostolos Zaravinos ◽

Ralitsa P. Iskrenova ◽

Agathoklis I. Psyrogiannis ◽

...

Keyword(s):

Gene Expression ◽

Microarray Analysis ◽

High Fat Diet ◽

Metabolic Regulation ◽

Expression Profiles ◽

Related Factor ◽

High Fat ◽

Qrt Pcr ◽

Nrf2 Knockout

Introduction. The transcription factor NFE2-related factor 2 (Nrf2) is a central regulator of antioxidant and detoxification gene expression in response to electrophilic or oxidative stress. Nrf2 has recently been shown to cross-talk with metabolic pathways, and its gene deletion protected mice from high-fat-diet-(HFD-) induced obesity and insulin resistance. This study aimed to identify potential Nrf2-regulated genes of metabolic interest by comparing gene expression profiles of livers of wild-type (WT) versus Nrf2 knockout (Nrf2-KO) mice after a long-term HFD.Methods. WT and Nrf2-KO mice were fed an HFD for 180 days; total RNA was prepared from liver and used for microarray analysis and quantitative real-time RT-PCR (qRT-PCR).Results. The microarray analysis identified 601 genes that were differentially expressed between WT and Nrf2-KO mice after long-term HFD. Selected genes, including ones known to be involved in metabolic regulation, were prioritized for verification by qRT-PCR:Cyp7a1andFabp5were significantly overexpressed in Nrf2-KO mice; in contrast,Car,Cyp2b10,Lipocalin 13,Aquaporin 8,Cbr3,Me1, andNqo1were significantly underexpressed in Nrf2-KO mice.Conclusion. Transcriptome profiling after HFD-induced obesity confirms thatNrf2is implicated in liver metabolic gene networks. The specific genes identified here may provide insights into Nrf2-dependent mechanisms of metabolic regulation.

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