scholarly journals Effects of High-Fat and High-Fat/High-Sucrose Diet-Induced Obesity on PVAT Modulation of Vascular Function in Male and Female Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jamaira A. Victorio ◽  
Daniele M. Guizoni ◽  
Israelle N. Freitas ◽  
Thiago R. Araujo ◽  
Ana P. Davel
Keyword(s):  
Vascular Function ◽  
Vascular Complications ◽  
Mesenteric Arteries ◽  
Chow Diet ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
High Sucrose

Increased adiposity in perivascular adipose tissue (PVAT) has been related to vascular dysfunction. High-fat (HF) diet-induced obesity models are often used to analyze the translational impact of obesity, but differences in sex and Western diet type complicate comparisons between studies. The role of PVAT was investigated in small mesenteric arteries (SMAs) of male and female mice fed a HF or a HF plus high-sucrose (HF + HS) diet for 3 or 5 months and compared them to age/sex-matched mice fed a chow diet. Vascular responses of SMAs without (PVAT-) or with PVAT (PVAT+) were evaluated. HF and HF + HS diets increased body weight, adiposity, and fasting glucose and insulin levels without affecting blood pressure and circulating adiponectin levels in both sexes. HF or HF + HS diet impaired PVAT anticontractile effects in SMAs from females but not males. PVAT-mediated endothelial dysfunction in SMAs from female mice after 3 months of a HF + HS diet, whereas in males, this effect was observed only after 5 months of HF + HS diet. However, PVAT did not impact acetylcholine-induced relaxation in SMAs from both sexes fed HF diet. The findings suggest that the addition of sucrose to a HF diet accelerates PVAT dysfunction in both sexes. PVAT dysfunction in response to both diets was observed early in females compared to age-matched males suggesting a susceptibility of the female sex to PVAT-mediated vascular complications in the setting of obesity. The data illustrate the importance of the duration and composition of obesogenic diets for investigating sex-specific treatments and pharmacological targets for obesity-induced vascular complications.

scholarly journals Carbonyl Reductase 1 Overexpression in Adipose Amplifies Local Glucocorticoid Action and Impairs Glucose Tolerance in Lean Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A806-A806
Author(s):  
Rachel Bell ◽  
Elisa Villalobos ◽  
Mark Nixon ◽  
Allende Miguelez-Crespo ◽  
Matthew Sharp ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Fat Mass ◽  
High Fat Diet ◽  
Fasting Glucose ◽  
High Fat ◽  
Male And Female ◽  
Over Expression ◽  
Female Mice ◽  
Diet Induced Obesity

Abstract Glucocorticoids play a critical role in metabolic homeostasis. Chronic or excessive activation of the glucocorticoid receptor (GR) in adipose tissue contributes to metabolic disorders such as glucose intolerance and insulin resistance. Steroid-metabolising enzymes in adipose, such as 11β-HSD1 or 5α-reductase, modulate the activation of GR by converting primary glucocorticoids into more or less potent ligands. Carbonyl reductase 1 (CBR1) is a novel regulator of glucocorticoid metabolism, converting corticosterone/cortisol to 20β-dihydrocorticosterone/cortisol (20β-DHB/F); a metabolite which retains GR activity. CBR1 is abundant in adipose tissue and increased in obese adipose of mice and humans1 and increased Cbr1 expression is associated with increased fasting glucose1. We hypothesised that increased Cbr1/20β-DHB in obese adipose contributes to excessive GR activation and worsens glucose tolerance. We generated a novel murine model of adipose-specific Cbr1 over-expression (R26-Cbr1Adpq) by crossing conditional knock-in mice with Adiponectin-Cre mice. CBR1 protein and activity were doubled in subcutaneous adipose tissue of male and female R26-Cbr1Adpq mice compared with floxed controls; corresponding to a two-fold increase 20β-DHB (1.6 vs. 4.2ng/g adipose; P=0.0003; n=5-7/group). There were no differences in plasma 20β-DHB or corticosterone. Bodyweight, lean or fat mass, did not differ between male or female R26-Cbr1Adpq mice and floxed controls. Lean male R26-Cbr1Adpq mice had higher fasting glucose (9.5±0.3 vs. 8.4±0.3mmol/L; P=0.04) and worsened glucose tolerance (AUC 1819±66 vs. 1392±14; P=0.03). Female R26-Cbr1Adpq mice also had a worsened glucose tolerance but fasting glucose was not altered with genotype. There were no differences in fasting insulin or non-esterified fatty acid between genotypes in either sex. Expression of GR-induced genes Pnpla2, Gilz and Per1, were increased in adipose of R26-Cbr1Adpq mice. Following high-fat diet induced obesity, no differences in bodyweight, lean or fat mass, with genotype were observed in male and female mice, and genotype differences in fasting glucose and glucose tolerance were abolished. In conclusion, adipose-specific over-expression of Cbr1 in lean male and female mice led to increased levels of 20β-DHB in adipose but not plasma, and both sexes having worsened glucose tolerance. The influence of adipose CBR1/20β-DHB on glucose tolerance was not associated with altered fat mass or bodyweight and was attenuated by high-fat diet-induced obesity. These metabolic consequences of Cbr1 manipulation require careful consideration given the wide variation in CBR1 expression in the human population, the presence of inhibitors and enhancers in many foodstuffs and the proposed use of inhibitors as an adjunct for cancer treatment regimens. Reference: Morgan et al., Scientific Reports. 2017; 7.

Sex Differences in the Relation Between Frailty and Endothelial Dysfunction in Old Mice

2021 ◽  
Author(s):  
Jazmin A Cole ◽  
Mackenzie N Kehmeier ◽  
Bradley R Bedell ◽  
Sahana Krishna Kumaran ◽  
Grant D Henson ◽  
...  
Keyword(s):  
Sex Differences ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Frailty Index ◽  
Mesenteric Arteries ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Age Related

Abstract Vascular endothelial function declines with age on average, but there is high variability in the magnitude of this decline within populations. Measurements of frailty, known as frailty index (FI), can be used as surrogates for biological age, but it is unknown if frailty relates to the age-related decline in vascular function. To examine this relation, we studied young (4-9 months) and old (23-32 months) C57BL6 mice of both sexes. We found that FI was greater in old compared with young mice, but did not differ between old male and female mice. Middle cerebral artery (MCA) and mesenteric artery endothelium-dependent dilation (EDD) also did not differ between old male and female mice; however, there were sex differences in the relations between FI and EDD. For the MCA, FI was inversely related to EDD among old female mice, but not old male mice. In contrast, for the mesenteric artery, FI was inversely related to EDD among old male mice, but not old female mice. A higher FI was related to a greater improvement in EDD with the superoxide scavenger TEMPOL in the MCAs for old female mice and in the mesenteric arteries for old male mice. FI related to mesenteric artery gene expression negatively for extracellular superoxide dismutase (Sod3) and positively for interleukin-1β (Il1b). In summary, we found that the relation between frailty and endothelial function is dependent on sex and the artery examined. Arterial oxidative stress and pro-inflammatory signaling are potential mediators of the relations of frailty and endothelial function.

scholarly journals Contractility of permeabilized rat vastus intermedius muscle fibres following high-fat, high-sucrose diet consumption

2021 ◽  
Author(s):  
Ian C Smith ◽  
Curtis Ostertag ◽  
Jennifer J O'Reilly ◽  
Jaqueline Lourdes Rios ◽  
Teja Klancic ◽  
...  
Keyword(s):  
Contractile Function ◽  
Force Production ◽  
Muscle Fibres ◽  
Chow Diet ◽  
High Fat ◽  
Force Output ◽  
Mhc I ◽  
Diet Induced Obesity ◽  
High Sucrose ◽  
Mhc Iia

Obesity is a worldwide health concern associated with impaired physical function. It is not clear if contractile protein dysfunction contributes to the impairment of muscle function observed with obesity. The purpose of this study was to examine if diet-induced obesity affects contractile function of chemically permeabilized vastus intermedius fibres of male Sprague Dawley rats expressing fast myosin heavy chain (MHC) IIa or slow MHC I. Rats consumed either a high-fat, high-sucrose (HFHS) diet or a standard (CHOW) diet beginning as either weanlings (7-week duration: WEAN7 cohort, or 14-week duration: WEAN14 cohort) or young adults (12-week duration: ADULT12 cohort, 24-week duration: ADULT24 cohort). HFHS-fed rats had higher (P<0.05) whole-body adiposity (derived from dual-energy X-ray absorptiometry) than CHOW-fed rats in all cohorts. Relative to CHOW diet groups, the HFHS diet was associated with impaired force production in a) MHC I fibres in the ADULT24 cohort, and b) MHC IIa fibres in the ADULT12 and ADULT24 cohorts combined. However, the HFHS diet did not significantly affect the Ca2+-sensitivity of force production, unloaded shortening velocity, or ratio of active force to active stiffness in any cohort. We conclude that diet-induced obesity can impair force output of permeabilized muscle fibres of adult rats. Novelty Bullets: • We assessed contractile function of permeabilized skeletal muscle fibres in a rat model of diet-induced obesity. • The high-fat, high-sucrose diet was associated with impaired force output of fibres expressing MHC I or MHC IIa in some cohorts of rats. • Other measures of contractile function were not significantly affected by diet.

scholarly journals Container-aided Integrative QTL and RNA-seq Analysis of Collaborative Cross Mice Supports Distinct Sex-Oriented Molecular Modes of Response in Obesity

2019 ◽  
Author(s):  
Ilona Binenbaum ◽  
Hanifa Abu-Toamih Atamni ◽  
Georgios Fotakis ◽  
Georgia Kontogianni ◽  
Theodoros Koutsandreas ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Complex Traits ◽  
Hepatic Gene Expression ◽  
High Fat ◽  
Mouse Population ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Genetic Mechanisms

Abstract Background: The CC mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, the underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population. Results: We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrate these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms. Conclusion: Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity differ in female and male mice. The clear distinction we observe in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.

scholarly journals Container-aided integrative QTL and RNA-seq analysis of Collaborative Cross mice supports distinct sex-oriented molecular modes of response in obesity

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ilona Binenbaum ◽  
Hanifa Abu-Toamih Atamni ◽  
Georgios Fotakis ◽  
Georgia Kontogianni ◽  
Theodoros Koutsandreas ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Complex Traits ◽  
Hepatic Gene Expression ◽  
High Fat ◽  
Mouse Population ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Genetic Mechanisms

Abstract Background The Collaborative Cross (CC) mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population. Results We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrated these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms. Conclusion Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity are different in female and male mice. The clear distinction we observed in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.

scholarly journals Container-aided Integrative QTL and RNA-seq Analysis of Collaborative Cross Mice Supports Distinct Sex-Oriented Molecular Modes of Response in Obesity

2020 ◽  
Author(s):  
Ilona Binenbaum ◽  
Hanifa Abu-Toamih Atamni ◽  
Georgios Fotakis ◽  
Georgia Kontogianni ◽  
Theodoros Koutsandreas ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Complex Traits ◽  
Hepatic Gene Expression ◽  
High Fat ◽  
Mouse Population ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Genetic Mechanisms

Abstract Background: The CC mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, the underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population. Results: We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrate these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms. Conclusion: Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity differ in female and male mice. The clear distinction we observe in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.

Glutaredoxin1 knockout promotes high-fat diet-induced obesity in male mice but not in female ones

2021 ◽  
Author(s):  
Xiao yu Zou ◽  
Muhammad Ijaz Ahmad ◽  
Di Zhao ◽  
Min Zhang ◽  
Chunbao Li
Keyword(s):  
High Fat Diet ◽  
Calorie Intake ◽  
Male Mice ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity

This study aims to explore how high-fat diet and glutaredoxin1 (Glrx1) deficiency affect the development of obesity in male and female mice. High-fat diet induced great differences in calorie intake...

scholarly journals Container-aided Integrative QTL and RNA-seq Analysis of Collaborative Cross Mice Supports Distinct Sex-Oriented Molecular Modes of Response in Obesity

2020 ◽  
Author(s):  
Ilona Binenbaum ◽  
Hanifa Abu-Toamih Atamni ◽  
Georgios Fotakis ◽  
Georgia Kontogianni ◽  
Theodoros Koutsandreas ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Complex Traits ◽  
Collaborative Cross ◽  
Hepatic Gene Expression ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Genetic Mechanisms

Abstract Background: The Collaborative Cross (CC) mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population.Results: We established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrated these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms.Conclusion: Integration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity are different in female and male mice. The clear distinction we observed in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.

scholarly journals Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns

2019 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Julie A. Allen ◽  
Colin S. McCoin ◽  
Qing Xia ◽  
...  
Keyword(s):  
Body Composition ◽  
Weight Gain ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Fat Mass ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
High Sucrose

ABSTRACTObjectiveLong-term weight gain can result from cumulative small weight increases due to short-term excess caloric intake during weekends and holidays. Increased physical activity may mediate weight gain through increases in energy expenditure (EE) and reductions in energy balance. Current methods for modulating mouse EE (e.g. – exercise, chemical uncouplers, etc.) have confounding effects. However, it is known that mouse EE linearly increases as housing temperature decreases below the thermoneutral zone.MethodsTo determine how robust differences in baseline EE impact 7-day changes in weight and body composition on low-fat and high-fat, high-sucrose (HFHS) diets, we performed indirect calorimetry measurements in male and female mice housed at divergent temperatures (20°C vs. 30°C).ResultsAs expected, mice housed at 30°C have ∼40% lower total EE and energy intake compared to 20°C mice regardless of diet or sex. Energy balance was increased with HFHS in all groups, with ∼30% greater increases observed in 30°C versus 20°C mice. HFHS increased weight gain regardless of temperature or sex. Interestingly, no HFHS-induced weight gain differences were observed between females at different temperatures. In contrast, 30°C male mice on HFHS gained ∼50% more weight than 20°C males, and ∼80% more weight compared to 30°C females. HFHS increased fat mass across all groups but 2-fold higher gains occurred in 30°C mice compared to 20°C mice. Females gained ∼35% less fat mass than males at both temperatures.ConclusionsTogether, these data reveal an interaction between divergent ambient temperature-induced EE and sex that impacted diet-induced patterns of short-term weight gain and body composition.HighlightsUtilized ambient temperature differences as an experimental tool to study the impact of divergent baseline energy expenditure on metabolic adaptation to high-fat, high-sucrose diet.Baseline energy expenditure and sex interact to impact diet-induced changes in body composition and weight gain.The energy expenditure and sex interaction is a result of an inverse relationship between fat mass gain and weight-adjusted total energy expenditure, as well as, diet-induced non-shivering thermogenesis.These data support that the hypothesis that higher energy expenditure amplifies the coupling of energy intake to energy expenditure during energy dense feeding, resulting in reduced positive energy balance and reduced gains in weight and adiposity.First evidence that energy expenditure level plays a role in the composition of weight gained by female mice during acute HFHS feeding.This study further highlights issues with obesity/energy metabolism research performed in mice at sub-thermoneutral housing temperatures, particularly with sex comparisons.GRAPHIC ABSTRACTLegend: Male and female mice housed at 30°C had lower energy expenditure (EE) & energy intake (EI), while having greater energy balance (EB), during 7-day high-fat/high-sucrose (HFHS) feeding compared to male and female mice, respectively, housed at 20°C. However, female mice had lower EB compared to males at both housing temperature. Female mice housed at 30°C gained less weight than 30°C males but gained the same relative amount of fat mass during acute HFHS feeding. Interestingly, 20°C females gained the same amount of weight as 20°C males but gained primarily fat-free mass, while the males gained the same proportion of fat as 30°C males and females.

scholarly journals Does gender influence cardiovascular remodeling in C57BL/6J mice fed a high-fat, high-sucrose, high-salt diet?

2018 ◽  
Author(s):  
Debora Cristina Pereira-Silva ◽  
Rayane Paula Machado-Silva ◽  
Camila Castro-Pinheiro ◽  
Caroline Fernandes-Santos
Keyword(s):  
Thoracic Aorta ◽  
Body Mass ◽  
High Salt ◽  
Heart Hypertrophy ◽  
Male Mice ◽  
High Fat ◽  
Male And Female ◽  
Cardiovascular Remodeling ◽  
Female Mice ◽  
High Sucrose

Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease was not exploited so far. Thus, this study investigated cardiovascular remodeling in C57BL/6J mice fed a diet rich in saturated fat, sucrose, and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose, and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodeling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance assessed by serum glucose, insulin, and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in male and female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta had intima-media thickening in male mice, but in the female, it was only noticed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Changes in LV dimensions and the arterial remodeling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodeling after 12 weeks of high-fat, high-sucrose, high-salt feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy, and intramyocardial artery remodeling.

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