Prolonged saturated, but not monounsaturated, high-fat feeding provokes anxiodepressive-like behaviors in female mice despite similar metabolic consequences

Abstract The circadian system is a critical regulator of obesity in male mice, but its role in females is poorly understood. In our previous studies we found that estrogen regulates daily rhythms in female mice to confer resistance to diet-induced obesity, but the mechanism is unknown. Estrogen signals via the classical estrogen receptor alpha (ERα) to regulate metabolism and obesity. Therefore, in this study we tested the hypothesis that estrogen regulates daily metabolic rhythms in females via ERα. To do so, we studied daily rhythms in female global ERα knockout (ERα KO) with the circadian reporter, PERIOD2::LUCIFERASE, mice fed high-fat diet for 6 weeks. ERα KO female mice became obese and hyperglycemic when fed high-fat diet, while wild-type females were resistant to diet-induced obesity. Chronic high-fat diet feeding also reduced the amplitude of the daily rhythm of eating behavior in ERα KO, but not wild-type, female mice. In wild-type females, the amplitude of the locomotor activity rhythm increased during high-fat feeding. In contrast, high-fat feeding decreased the amplitude of the activity rhythm in ERα KO females. The temporal relationship between central and peripheral circadian tissue clocks was disrupted by high-fat feeding in ERα KO females since the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced 4 hours by high-fat feeding in ERα KO mice compared to wild-type females. Taken together these results show that estrogen signals via ERα to protect daily metabolic rhythms from disruption by high-fat feeding in female mice.

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Abstract 10: Mouse Recombinant Soluble PRR-induced Increase Of Blood Pressure Is Sex-dependant In High Fat-fed Mice

Hypertension ◽

10.1161/hyp.76.suppl_1.10 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Audrey A Poupeau ◽

Eva Gatineau ◽

Gertrude Arthur ◽

Wen Su ◽

Ming C Gong ◽

...

Keyword(s):

Blood Pressure ◽

Renin Angiotensin System ◽

The Body ◽

Soluble Form ◽

Dependent Manner ◽

High Fat ◽

Female Mice ◽

Prorenin Receptor ◽

Atropine Treatment ◽

Fat Feeding

Obesity is a major risk factor for hypertension. Although the renin-angiotensin system (RAS) contributes to the sex difference of blood pressure (BP) control, whether the prorenin receptor (PRR) and its soluble form (sPRR) play a role in the sexual dimorphism of BP is not clear. We previously demonstrated that, in high fat (HF)-fed male C57BL/6 mice, the infusion of mouse recombinant sPRR increased systolic blood pressure (SBP) by the sympatho-excitatory effects of leptin on BP. Therefore, in the present study, we aim to address whether mouse recombinant sPRR influences the BP in HF-fed female mice. To test this hypothesis, C57BL/6 female mice were fed a HF diet for 32 weeks and were implanted with radiotelemetry transmitter. After 24 weeks of high fat feeding, female mice (5-6/group) were implanted with osmotic pumps and infused with either saline (veh) or sPRR for 3 to 4 weeks. In contrast to male mice, the infusion of sPRR (30 μg/kg/day) did not change significantly the SBP (24hSBP; veh: 135 ± 7; sPRR: 134 ± 4 mmHg; P>0.05) and the baroreflex sensitivity. The decrease in BP mediated by chlorisondamine treatment was not significantly different between female mice infused with vehicle or sPRR (ΔSBP; veh: -11 ± 9; sPRR: -16 ± 7 mmHg; P>0.05). In addition, sPRR infusion did not affect the bradycardic or tachycardic responses after propranolol or atropine treatment respectively. Moreover, the decrease of SBP induced by losartan was similar in mice infused with vehicle or sPRR (ΔSBP; veh: -9 ± 4; sPRR: -10 ± 3 mmHg; P>0.05). Similar results were obtained using higher dose of sPRR (60 μg/kg/day). In female mice, sPRR infusion did not increase significantly the body weight (veh: 32.7 ± 2.5 g; sPRR: 35.8 ± 4.2 g; P>0.05), the white adipose tissue weight (WAT; veh: 3.0 ± 0.7g; sPRR: 3.7 ± 1.6 g; P>0.05) or circulating leptin levels (veh: 12.0 ± 7.6 ng/ml; sPRR: 15.5 ± 9.5 ng/ml; P>0.05). In conclusion, in contrast to male, female mice are protected from sPRR-induced increase in BP. sPRR did not increase circulating leptin suggesting that sPRR-induced leptin increase is regulated in a sex-dependent manner. Other pathways could participate to the protection against sPRR-induced increase in BP in female mice such as the vasodilator arm of the RAS and/or the hormonal status of the female mice.

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Pre- and Post-natal High Fat Feeding Differentially Affects the Structure and Integrity of the Neurovascular Unit of 16-Month Old Male and Female Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2019.01045 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 2

Author(s):

Laura Contu ◽

Shereen Nizari ◽

Christopher J. Heath ◽

Cheryl A. Hawkes

Keyword(s):

Neurovascular Unit ◽

High Fat ◽

Male And Female ◽

Female Mice ◽

Fat Feeding

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1759-P: Effects of High-Fat Feeding on Adipose Tissue Matrisome Composition in Female Mice

Diabetes ◽

10.2337/db19-1759-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1759-P

Author(s):

JENNIFER L. BAILEY ◽

CARRIE M. ELKS

Keyword(s):

Adipose Tissue ◽

High Fat ◽

Female Mice ◽

Fat Feeding

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Adverse Effects of AMP-Activated Protein Kinase α2-Subunit Deletion and High-Fat Diet on Heart Function and Ischemic Tolerance in Aged Female Mice

Physiological Research ◽

10.33549/physiolres.932979 ◽

2016 ◽

pp. 33-42 ◽

Cited By ~ 7

Author(s):

K. SLÁMOVÁ ◽

F. PAPOUŠEK ◽

P. JANOVSKÁ ◽

J. KOPECKÝ ◽

F. KOLÁŘ

Keyword(s):

Protein Kinase ◽

Adverse Effects ◽

Infarct Size ◽

Heart Function ◽

Left Ventricular ◽

Ischemic Tolerance ◽

High Fat ◽

Female Mice ◽

Amp Activated Protein Kinase ◽

Fat Feeding

AMP-activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK α2-subunit deletion affects heart function and ischemic tolerance of adult and aged mice. AMPK α2-/- (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK α2-subunit protein level, but no difference in AMPK α1-subunit was detected between the strains. Both α1- and α2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK α2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive.

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