Abstract P271: Delineating Sex-specific Mechanisms Of Impaired Vasoreactivity In Thermoneutrality

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ji Hye Chun ◽  
Melissa M Henckel ◽  
Leslie A Knaub ◽  
Lori A Walker ◽  
Jane E Reusch ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Rat Aorta ◽  
Female Rats ◽  
Ex Situ ◽  
Dependent Manner ◽  
Perivascular Adipose Tissue ◽  
Male And Female ◽  
Male And Female Rats ◽  
Brown Adipose

Cardiovascular disease (CVD) is a leading cause of hospitalization and death. CVD is characterized by impaired vasoreactivity and mitochondrial dysfunction. Perivascular adipose tissue (PVAT), considered brown adipose tissue (BAT), surrounds the vasculature and regulates its response. Preliminary data with rats housed at either their thermoneutrality (TN, 30°C) or room temperature (RT, 22°C) showed diminished vasodilation in aorta from TN rats as compared with those from RT rats (10.2% ± 4.0% (0.159 g of vasodilation capacity, starting from maximal force constriction of 1.563 g) versus 64.2% ± 5.3% (0.909 g of 1.417 g, p<0.001). TN-housed rat aorta also showed less mitochondrial respiration with lipid substrates in multiple states (p<0.05). We hypothesize that remodeling of PVAT phenotype from BAT to white adipose tissue (WAT) may alter mitochondrial lipid utilization and cause vasoreactivity dysfunction. To test this, we housed male and female rats at either RT or TN and investigated their own PVAT + aorta or PVAT from the oppositely- housed animals along with each rat’s own aorta for vasoreactivity ex situ. There was diminished vasodilation in all TN animals with PVAT + aorta (29.2% ± 3.8% (0.269 g of 0.923 g) versus 37.6% ± 6.0% (0.255 g of 0.677 g), p<0.02), with only male animals showing a significant effect from PVAT (p<0.001). In aorta of TN-housed animals analyzed with PVAT from RT-housed animals, female vessels showed an increase in vasodilation capacity as compared to controls (56.8% ± 13.6% (0.589 g of 1.037 g) versus 5.2% ± 2.3% (0.028 g of 0.534 g), p<0.001), strongly suggesting that PVAT not only regulates vasoreactivity, but can repair TN-induced diminished dilation in a sex-dependent manner. All animals at TN had significantly less mitochondrial respiration with lipid substrates (p<0.05), with no sex differences. We further observed a significantly greater amount of lipids in PVAT from male TN-housed animals as compared to that in RT-housed animals (p<0.05), consistent with a WAT phenotype. Our data support that TN alters PVAT phenotype in a sex-dependent manner, resulting in dysfunctional vasoreactivity and mitochondrial function. These targets of CVD in both male and female animals are exciting avenues for novel therapeutics.

Early weaning alters the thermogenic capacity of brown adipose tissue in adult male and female rats

2019 ◽  
Vol 59 (5) ◽  
pp. 2207-2218 ◽  
Author(s):  
T. C. Peixoto ◽  
C. B. Pietrobon ◽  
I. M. Bertasso ◽  
F. A. H. Caramez ◽  
C. Calvino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adult Male ◽  
Female Rats ◽  
Early Weaning ◽  
Male And Female ◽  
Male And Female Rats ◽  
Brown Adipose ◽  
Thermogenic Capacity

Sex difference in insulin-stimulated glucose transport in rat and human adipocytes

1984 ◽  
Vol 246 (3) ◽  
pp. E211-E215 ◽  
Author(s):  
J. E. Foley ◽  
A. Kashiwagi ◽  
H. Chang ◽  
T. P. Huecksteadt ◽  
S. Lillioja ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Transport ◽  
Subcutaneous Tissue ◽  
Subcutaneous Fat ◽  
Transport Rate ◽  
Female Rats ◽  
Fat Tissue ◽  
Male And Female ◽  
Male And Female Rats ◽  
Female Subjects

In an effort to determine whether differences in basal and maximum insulin-stimulated glucose transport by isolated adipocytes are a function of donor sex, we measured glucose transport rates in the absence and presence of 8 nM insulin in adipocytes isolated from the abdominal subcutaneous fat tissue of nine male and ten female subjects with varying degrees of obesity and in adipocytes isolated from the abdominal subcutaneous and retroperitoneal fat tissue of (180-220 g) male and female rats. Because maximal insulin-stimulated glucose transport rate per cell of adipocytes isolated from subcutaneous abdominal tissue of male and female subjects was constant in each sex, the data have been normalized on the basis of transport per cell. The results demonstrated that basal and maximal insulin-stimulated glucose transport per cell was 53-75% higher per cell in the females versus males in adipocytes from human subcutaneous abdominal adipose tissue (P less than 0.01). A similar difference in glucose transport rate between males and females (P less than 0.001) was also found in rat abdominal subcutaneous adipose tissue. Adipocytes isolated from rat retroperitoneal adipose tissue had higher transport rates (approximately three-fold) and smaller sex differences (35% higher in females) than found in adipocytes from rat and human subcutaneous tissue. These results indicate that basal and maximum insulin-stimulated glucose transport is higher by adipocytes isolated from females and that this difference is independent of adipose cell size and species.

scholarly journals Chronic Stress During Adolescence Blunts the Exercise-Induced Expression of Thyroid Hormone-Target Genes in Metabolically Active Tissues of Male and Female Rats

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A974-A974
Author(s):  
Marco Antonio Parra-Montes de Oca ◽  
Karen Lissette Garduño-Morales ◽  
Patricia Joseph-Bravo
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Chronic Stress ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Dependent Manner ◽  
Male And Female ◽  
Male And Female Rats ◽  
Exercise Induced ◽  
Hpt Axis

Abstract Voluntary exercise activates HPT axis1, that contributes to energy mobilization and energy expenditure. Chronic stress in adulthood inhibits HPT response to voluntary wheel running in a sex dependent manner, inhibiting lipolysis of WAT2. We evaluated the effect of chronic stress during adolescence on HPT axis response to voluntary exercise in adulthood3, with emphasis on metabolic response in skeletal muscle and WAT. Wistar male and female rats (N=36 per sex) were divided in an undisturbed group (Control, C; n=18) and one chronic variable stress during adolescence group (CVS; n=18) (males: PND 30-70; females: PND 30-60). As adults (males: PND 84; females: PND: 74) rats were divided in: 1) exercise group: rats placed individually in a cage with a running wheel per 14 nights, 2) sedentary group with ad libitum feeding, 3) sedentary pair-fed group offered the same amount of food consumed by the exercised group, and kept in individual cages during 14 nights (6 rats/group). WAT weight was determined at sacrifice, hormones quantified by RIA and ELISA, gene expression by RT-PCR. Exercise-induced loss of fat mass was not detected in CVS rats. Exercise decreased corticosterone levels in C males and females of both treatments, supporting sex difference on HPA axis reprogramming by CVS. HPT axis response to voluntary exercise is attenuated by CVS also in a sex dimorphic manner: CVS decreased Trh expression in hypothalamic paraventricular nucleus and no changes in thyroid hormones concentration in males, whereas in females, slightly increased TSH, T4 and T3 levels. Sex also influenced the response of skeletal muscle and WAT to CVS. Dio2 and Pgc1a slightly increased expression in skeletal muscle of males, not of females. Adrb3 expression in WAT increased in females, but not in males; exercise-induced stimulation of Hsl expression was not observed in either sex after CVS. These results suggest that CVS imposed during rat adolescence inhibits the responses to voluntary exercise of HPT axis activity of thyroid hormone-targets in WAT and skeletal muscle in sex dependent manner. These changes could lead to reduced mobilization and the utilization of energy fuels coincident with the fatigue observed after exercise in patients with subclinical or clinical hypothyroidism. (Funded: CONACYT 284883, DGAPA IN213419)1Uribe, Endocrinology 155:2020-2030, 2014.2Parra, Front Endocrinol 10(418):1-13, 2019.3Parra, J Endocr Soc 4(Abstract Supp) Abstract SAT-451, 2020.

scholarly journals Blockage of the Neonatal Leptin Surge Affects the Gene Expression of Growth Factors, Glial Proteins, and Neuropeptides Involved in the Control of Metabolism and Reproduction in Peripubertal Male and Female Rats

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2571-2581 ◽  
Author(s):  
Virginia Mela ◽  
Francisca Díaz ◽  
Ana Belen Lopez-Rodriguez ◽  
María Jesús Vázquez ◽  
Arieh Gertler ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Pubertal Development ◽  
Trophic Factors ◽  
Female Rats ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Male And Female ◽  
Male And Female Rats ◽  
Subcutaneous Adipose

Leptin (Lep) is important in the development of neuroendocrine circuits involved in metabolic control. Because both Lep and metabolism influence pubertal development, we hypothesized that early changes in Lep signaling could also modulate hypothalamic (HT) systems involved in reproduction. We previously demonstrated that a single injection of a Lep antagonist (Antag) on postnatal day (PND)9, coincident with the neonatal Lep peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the HT on PND13. Here, our aim was to investigate whether the alterations induced by Lep antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super Lep Antag from PND5 to PND9 and killed just before the normal appearance of external signs of puberty (PND33 in females and PND43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and HT neuropeptide Y and Agouti-related peptide mRNA levels were reduced, with no effect in females. In both sexes, the Antag increased HT mRNA levels of the kisspeptin receptor, G protein-coupled recepter 54 (Gpr54). Expression of the Lep receptor, trophic factors, and glial markers were differently affected in the HT of peripubertal males and females. Lep production in adipose tissue was decreased in Antag-treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal Lep levels modifies factors involved in reproduction that could possibly affect sexual maturation.

scholarly journals Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring

2017 ◽  
Vol 118 (10) ◽  
pp. 788-803 ◽  
Author(s):  
Mariana M. Almeida ◽  
Camilla P. Dias-Rocha ◽  
André S. Souza ◽  
Mariana F. Muros ◽  
Leonardo S. Mendonca ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Content ◽  
Endocannabinoid System ◽  
Female Rats ◽  
Developmental Origins ◽  
High Fat ◽  
Male And Female ◽  
Rat Offspring ◽  
Brown Adipose

AbstractPerinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS’s components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

scholarly journals Effect of Methadone on Lipid Profile, Serum Leptin and Liver Enzymes Levels in Male and Female Rats

2021 ◽  
Vol 12 (5) ◽  
pp. 6428-6436
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol ◽  
Liver Enzymes ◽  
Density Lipoprotein ◽  
Female Rats ◽  
Metabolic Effects ◽  
Dependent Manner ◽  
Male And Female ◽  
Male And Female Rats ◽  
Significant Difference

Methadone Maintenance Therapy (MMT) has been accepted as a gold-standard treatment for opioid therapy. It may associate with adverse effects. This study aimed to affect methadone on serum lipid profile, leptin levels, and liver enzymes in male and female rats. 41 Wistar rats weighing 200-300gr were randomly assigned into four groups, including two methadone treatments and two control groups, both male and female, that received 5mg/kg methadone or 1cc normal saline daily for 8 weeks respectively by gavage method. All animals were weighed weekly. Fasting blood sugar (FBS) was measured by a glucometer, and blood samples were taken by cardiac puncture for triglyceride, low-density lipoprotein (LDL),high-density lipoprotein (HDL), total cholesterol, Aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) and leptin levels measurement after 12h fasting. One-way ANOVA showed no significant difference in mean FBS, total cholesterol, triglyceride, and LDL levels among the four groups. Moreover, there was a statistically significant difference in the mean of HDL, ALT, AST, and ALP levels. Furthermore, repeated measures ANOVA indicated a significant increase in body weight of rats during 8 weeks. Our findings indicated changes in some metabolic effects associated with methadone treatment in a gender-dependent manner.

Abstract WP102: Cerebrolysin Improves Neurological Outcome in Rats After Acute Stroke: a Prospective, Randomized, Blinded, Placebo-controlled Study

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Mei Lu ◽  
Talan Zhang ◽  
Pardeep Pabla ◽  
...  
Keyword(s):  
Neurological Outcome ◽  
Infarct Volume ◽  
Female Rats ◽  
Dose Effect ◽  
Functional Improvement ◽  
Controlled Study ◽  
Lesion Volume ◽  
Dependent Manner ◽  
Male And Female ◽  
Male And Female Rats

Background and Purpose: Cerebrolysin is a mixture of neuropeptides and free amino acids that exert potent neuroprotective and neurorestorative properties in experimental models of stroke. We conducted a prospective, randomized, double-blind and placebo controlled dose-response study of Cerebrolysin in both male and female rats after embolic stroke. Methods: Randomization schemas were generated using nQuery3.0. Male and female Wistar rats (3-4 months) were subjected to embolic middle cerebral artery occlusion (MCAO). After confirming successful stroke with a 5 point neurological scale (Longa scale) at 3h after MCAO, ischemic rats were treated with Cerebrolysin at doses of (0.8, 2.5, 5.0, 7.5ml/kg) and saline based on the randomization schema 4h after MCAO and continued daily for a total of 10 consecutive days. The primary outcome was neurologic outcome measured by adhesive removal test, foot-fault test, and modified neurological severity score at day 28, lesion volume and mortality were secondary and safety outcomes, respectively. Results: There was a significant dose effect of Cerebrolysin on neurological functional improvement 28 day after MCAO. Cerebrolysin at a dose of ≥ 2.5ml/kg significantly (P<0.001) improved neurological outcome (Mean Estimate with 95%CL): 0.8ml/kg: 6.2 (-6.0/18.4), 2.5ml/kg: -28.9 (-41.6/-16.2), 5.0ml/kg: -33.4 (-45.0/-21.7), 7.5ml/kg: -36.3 (-48.2/-24.4). Higher doses (≥2.5ml/kg) resulted in better recovery; however, differences between effective doses were not significant. Treatment with 5ml/kg reduced lesion volume (19.5±8.9%) compared with saline treated rats (27.7±11.9%, P=0.016). No treatment gender interactions were found and there were no differences on mortality rate. Conclusion: Cerebrolysin in a dose-dependent manner significantly improved neurological outcomes in ischemic rats. Cerebrolysin at a dose of 5ml/kg reduced infarct volume. Our data on Cerebrolysin efficacy demonstrate the feasibility of a preclinical study setup following a randomized, placebo controlled, and blinded design with a clinical relevant treatment scheme.

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