Consuming a balanced high fat diet for 16 weeks improves body composition, inflammation and vascular function parameters in obese premenopausal women

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that improves insulin sensitivity, glucose tolerance, and energy balance in obese rodents. Our recent findings suggest that Ang-(1-7) activates mas receptors (MasR) in the arcuate nucleus of the hypothalamus (ARC), a brain region critical to control of energy balance and glucose homeostasis, to induce these positive metabolic effects. The distribution of MasR in the ARC and their role in metabolic regulation, however, is unknown. We hypothesized: (1) MasR are expressed in the ARC; and (2) deletion of ARC MasR leads to worsened metabolic outcomes following high fat diet (HFD). To test this, male and female C57Bl/6J mice were fed a 60% HFD or matched control diet ad libitum for 12 weeks. RNAscope in situ hybridization was performed on coronal ARC sections in rostral-middle-caudal regions to determine percentage of MasR positive neurons (n=5/group). In a second experiment, we assessed body composition and insulin and glucose tolerance in transgenic mice with deletion of MasR in ARC neurons (MasR-flox with AAV5-hsyn-GFP-Cre). RNAscope revealed a wide distribution on MasR-positive cells throughout the rostral to caudal extent of the ARC. The average percentage of MasR positive neurons was increased in females versus males, with HFD tending to increase MasR expression in both sexes (control diet male: 11±2; control diet female: 17±3; HFD male: 15±5; HFD female: 24±2; p sex : 0.030; p diet : 0.066; p int : 0.615; two-way ANOVA). Deletion of MasR in ARC neurons worsened insulin sensitivity in HFD but not control diet females (area under the curve for change in glucose from baseline: -1989±1359 HFD control virus vs. 2530±1762 HFD Cre virus; p=0.016), while fasting glucose, glucose tolerance, and body composition did not change. There was no effect of ARC MasR deletion on metabolic outcomes in control diet or HFD male mice. These findings suggest females have more MasR positive neurons in the ARC compared to males, which may be a sex-specific protective mechanism for glucose homeostasis. While further studies are needed to explore the role of ARC MasR in metabolic regulation, these findings support targeting Ang-(1-7) as an innovative strategy in obesity.

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Maternal separation enhances anticontractile perivascular adipose tissue function in male rats on a high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00197.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. R1085-R1095 ◽

Cited By ~ 1

Author(s):

Analia S. Loria ◽

Frank T. Spradley ◽

Ijeoma E. Obi ◽

Bryan K. Becker ◽

Carmen De Miguel ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Life Stress ◽

Vascular Function ◽

Maternal Separation ◽

Male Rats ◽

Protective Effects ◽

Ang Ii ◽

High Fat ◽

Perivascular Adipose Tissue

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.

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Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet

Nutrition Research ◽

10.1016/j.nutres.2009.10.003 ◽

2009 ◽

Vol 29 (11) ◽

pp. 784-793 ◽

Cited By ~ 119

Author(s):

Nora Chen ◽

Rebecca Bezzina ◽

Edward Hinch ◽

Paul A. Lewandowski ◽

David Cameron-Smith ◽

...

Keyword(s):

Gene Expression ◽

Body Composition ◽

Glucose Tolerance ◽

Green Tea ◽

High Fat Diet ◽

Black Tea ◽

High Fat ◽

Metabolic Gene ◽

Metabolic Gene Expression ◽

Improve Glucose Tolerance

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Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents

International Journal of Molecular Sciences ◽

10.3390/ijms20030499 ◽

2019 ◽

Vol 20 (3) ◽

pp. 499 ◽

Cited By ~ 6

Author(s):

Michela Zanetti ◽

Gianluca Gortan Cappellari ◽

Andrea Graziani ◽

Rocco Barazzoni

Keyword(s):

Oxidative Stress ◽

Lipid Accumulation ◽

High Fat Diet ◽

Vascular Function ◽

Vascular Dysfunction ◽

High Fat ◽

Enos Expression ◽

Unacylated Ghrelin ◽

Vascular Oxidative Stress ◽

Expression And Activity

Unacylated ghrelin (UnGhr) exerts several beneficial actions on vascular function. The aim of this study was to assess the effects of UnGhr on high-fat induced endothelial dysfunction and its underlying mechanisms. Thoracic aortas from transgenic mice, which were overexpressing UnGhr and being control fed either a standard control diet (CD) or a high-fat diet (HFD) for 16 weeks, were harvested and used for the assessment of vascular reactivity, endothelial nitric oxide synthase (eNOS) expression and activity, thiobarbituric acid reactive substances (TBARS) and glutathione levels, and aortic lipid accumulation by Oil Red O staining. Relaxations due to acetylcholine and to DEA-NONOate were reduced (p < 0.05) in the HFD control aortas compared to vessels from the CD animals. Overexpression of UnGhr prevented HFD-induced vascular dysfunction, while eNOS expression and activity were similar in all vessels. HFD-induced vascular oxidative stress was demonstrated by increased (p < 0.05) aortic TBARS and glutathione in wild type (Wt) mice; however, this was not seen in UnGhr mice. Moreover, increased (p < 0.05) HFD-induced lipid accumulation in vessels from Wt mice was prevented by UnGhr overexpression. In conclusion, chronic UnGhr overexpression results in improved vascular function and reduced plaque formation through decreased vascular oxidative stress, without affecting the eNOS pathway. This research may provide new insight into the mechanisms underlying the beneficial effects of UnGhr on the vascular dysfunction associated with obesity and the metabolic syndrome.

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Evaluation of iNSiGHT VET DXA (Dual-Energy X-ray Absorptiometry) for assessing body composition in obese rats fed with high fat diet: a follow-up study of diet induced obesity model for 8 weeks

Laboratory Animal Research ◽

10.1186/s42826-019-0004-2 ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 1

Author(s):

Jungyun Yeu ◽

Han-Jik Ko ◽

Doyeun Kim ◽

Youngbok Ahn ◽

Jaejin Kim ◽

...

Keyword(s):

Body Composition ◽

High Fat Diet ◽

Dual Energy ◽

High Fat ◽

X Ray ◽

Follow Up Study ◽

Diet Induced Obesity ◽

Obese Rats

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Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000154 ◽

2014 ◽

Vol 5 (3) ◽

pp. 229-239 ◽

Cited By ~ 10

Author(s):

K. M. Platt ◽

R. J. Charnigo ◽

K. J. Pearson

Keyword(s):

Body Composition ◽

Body Weight ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

High Fat Diet ◽

High Fat ◽

High Fat Diets ◽

Normal Glucose ◽

Fat Diets

Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10–11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10–11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.

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