Transendothelial Insulin Transport is Impaired in Skeletal Muscle Capillaries of Obese Male Mice

ABSTRACTDelivery of insulin to the surface of myocytes is required for skeletal muscle (SkM) insulin action. Previous studies have shown that SkM insulin delivery is reduced in the setting of obesity and insulin resistance (IR). The key variables that control SkM insulin delivery are 1) microvascular perfusion and 2) the rate at which insulin moves across the continuous endothelium of SkM capillaries. Obesity and IR are associated with reduced insulin-stimulated SkM perfusion. Whether an impairment in trans-endothelial insulin transport (EIT) contributes to SkM IR, however, is unknown. We hypothesized that EIT would be delayed in a mouse model of diet-induced obesity (DIO) and IR. Using intravital insulin imaging, we found that DIO male mice have a ~15% reduction in EIT compared to their lean counterparts. This impairment in EIT is associated with a 45% reduction in the density of endothelial vesicles. Despite impaired EIT, hyperinsulinemia sustained delivery of insulin to the interstitial space in DIO male mice. Even with maintained interstitial insulin delivery DIO male mice still showed SkM IR, indicating severe myocyellular IR in this model. Interestingly, there was no difference in EIT, endothelial ultrastructure or SkM insulin sensitivity between lean and high fat diet-fed female mice. These results suggest that, in male mice, obesity results in damage to the capillary endothelium which limits the capacity for EIT.

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Effect of annatto-extracted tocotrienols and green tea polyphenols on glucose homeostasis and skeletal muscle metabolism in obese male mice

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2019.01.021 ◽

2019 ◽

Vol 67 ◽

pp. 36-43 ◽

Cited By ~ 5

Author(s):

Eunhee Chung ◽

Salvatore N. Campise ◽

Hayli E. Joiner ◽

Michael D. Tomison ◽

Gurvinder Kaur ◽

...

Keyword(s):

Skeletal Muscle ◽

Green Tea ◽

Glucose Homeostasis ◽

Muscle Metabolism ◽

Tea Polyphenols ◽

Green Tea Polyphenols ◽

Male Mice ◽

Skeletal Muscle Metabolism ◽

Obese Male

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FERTILITY IN GOLDTHIOGLUCOSE OBESE MALE MICE AND INFERTILITY IN BROWN HEREDITARY OBESE MALE MICE BEFORE AND DURING FORCED EXERCISE

Acta Endocrinologica ◽

10.1530/acta.0.067s233 ◽

1971 ◽

Vol 68 (1_Supplb) ◽

pp. S233

Author(s):

Niels Einer-Jensen

Keyword(s):

Male Mice ◽

Obese Male

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Androgenic and estrogenic regulation of skeletal muscle mass and atrophy signaling in male mice

Endocrine Abstracts ◽

10.1530/endoabs.32.p968 ◽

2013 ◽

Author(s):

Naeyer Helene De ◽

Inge Everaert ◽

Spaey Annelies De ◽

Jean-Marc Kaufman ◽

Youri Taes ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Male Mice ◽

Estrogenic Regulation

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Ultrastructural changes in skeletal muscle capillaries caused by snake venom and two of its fractions

Toxicon ◽

10.1016/0041-0101(85)90307-1 ◽

1985 ◽

Vol 23 (4) ◽

pp. 603

Keyword(s):

Skeletal Muscle ◽

Snake Venom ◽

Ultrastructural Changes ◽

Muscle Capillaries

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Abstract P199: Mas Receptor Deficiency Regulates Obesity-Hypertension and Cardiac Function in Female and Male Mice

Hypertension ◽

10.1161/hyp.68.suppl_1.p199 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Robin C Shoemaker ◽

Yu Wang ◽

Sean Thatcher ◽

Lisa Cassis

Keyword(s):

Blood Pressure ◽

Sexual Dimorphism ◽

Cardiac Function ◽

Male Mice ◽

Reduced Ejection Fraction ◽

Obesity Hypertension ◽

Obese Male ◽

Deficient Mice ◽

Cmr Imaging

Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male versus ( vs ) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female MasR +/+ and -/- mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male MasR +/+ mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed MasR -/- mice exhibited reduced DBP compared to HF-fed MasR +/+ males (90 ± 1 vs 96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male MasR -/- mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding. MasR -/- mice had significantly reduced ejection fraction (EF) compared to MasR +/+ mice at baseline (51.4 ± 2.5 vs 59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4 vs 52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in MasR -/- mice with 1 month of HF-feeding. MasR +/+ , but not MasR -/- mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.

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Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00107.2003 ◽

2003 ◽

Vol 285 (4) ◽

pp. E876-E888 ◽

Cited By ~ 193

Author(s):

Suzanne Reisz-Porszasz ◽

Shalender Bhasin ◽

Jorge N. Artaza ◽

Ruoqing Shen ◽

Indrani Sinha-Hikim ◽

...

Keyword(s):

Skeletal Muscle ◽

Transgenic Mice ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Fluorescent Protein ◽

Male Mice ◽

Wild Type ◽

Specific Expression ◽

Muscle Weight ◽

Myostatin Gene

Mutations in the myostatin gene are associated with hypermuscularity, suggesting that myostatin inhibits skeletal muscle growth. We postulated that increased tissue-specific expression of myostatin protein in skeletal muscle would induce muscle loss. To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA. Transgenic mice harboring these MCK promoters linked to enhanced green fluorescent protein (EGFP) expressed the reporter protein only in skeletal and cardiac muscles (MCK) or in skeletal muscle alone (MCK-3E). Seven-week-old animals were genotyped by PCR of tail DNA or by Southern blot analysis of liver DNA. Myostatin mRNA and protein, measured by RT-PCR and Western blot, respectively, were significantly higher in gastrocnemius, quadriceps, and tibialis anterior of MCK/Mst-transgenic mice compared with wild-type mice. Male MCK/Mst-transgenic mice had 18–24% lower hind- and forelimb muscle weight and 18% reduction in quadriceps and gastrocnemius fiber cross-sectional area and myonuclear number (immunohistochemistry) than wild-type male mice. Male transgenic mice with mutated MCK-3E promoter showed similar effects on muscle mass. However, female transgenic mice with either type of MCK promoter did not differ from wild-type controls in either body weight or skeletal muscle mass. In conclusion, increased expression of myostatin in skeletal muscle is associated with lower muscle mass and decreased fiber size and myonuclear number, decreased cardiac muscle mass, and increased fat mass in male mice, consistent with its role as an inhibitor of skeletal muscle mass. The mechanism of gender specificity remains to be clarified.

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Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Animals ◽

10.3390/ani11113187 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3187

Author(s):

Eunkuk Park ◽

Chang-Gun Lee ◽

Hyoju Jeon ◽

Hyesoo Jeong ◽

Subin Yeo ◽

...

Keyword(s):

High Fat Diet ◽

Insulin Action ◽

Normal Diet ◽

Male Mice ◽

Impaired Glucose Metabolism ◽

High Fat ◽

Beneficial Effects ◽

Cornus Officinalis ◽

Treatment And Prevention ◽

Obese Male

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

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