Obesity blunts insulin sensitivity improvements and attenuates strength gains following resistance training in nondiabetic men.

PURPOSE: Impaired insulin sensitivity is central in the etiology of type 2 diabetes in people with obesity. The effectiveness of resistance training (RE) alone in improving insulin sensitivity in people with obesity is undetermined. This study aimed to determine the influence of obesity on insulin sensitivity responses to RE. METHODS: Nineteen sedentary men were allocated to Lean (BMI 22.7 ± 2.5 kg m-2; n = 10) or Obese group (BMI 33.2 ± 3.2 kg m-2; n = 9). Participants were evaluated before and after a 10-week supervised progressive RE (3 sets of 10 repetition maximum (RM), 3 d/wk) for insulin sensitivity indexes using an oral glucose tolerance test, body composition using anthropometrics, and strength using 1RM. RESULTS: Groups were matched at baseline for all variables except for body composition and absolute strength. Body fat was not changed in both groups. Matsuda insulin sensitivity index, hepatic insulin resistance, and insulin area under the curve improved by 64.3 ± 61.9 unit, - 58.2 ± 102.9 unit, 2.3 ± 4.1 unit, and - 721.6 ± 858.2 µU/ml, respectively, only in the Lean group. The increased 1RM% for leg press was greater in the Lean (49.5 ± 18.7%) than in the Obese (31.5 ± 13.9), but not different for bench press (18.0 ± 9.1% vs. 16.4 ± 6.0%, respectively). CONCLUSION: Sustained obesity precludes insulin sensitivity improvements and attenuates strength gains in response to progressive RE. Additional strategies such as caloric restriction might be necessary for RE to improve insulin sensitivity, particularly at high levels of obesity.

Investigating the fate and toxicity of green synthesized gold nanoparticles in albino mice.

OBJECTIVE: This study aims to investigate the acute and chronic adverse effects of ∼50 nm (nanometer) gold nanoparticles (AuNPs) synthesized using Ziziphus zizyphus leaf extract in mice. SIGNIFICANCE: AuNPs have shown promise for medical applications, but their safety and biocompatibility need to be addressed. Understanding the potential adverse effects of AuNPs is crucial to ensure their safe use in medical applications. METHODS: The ∼50 nm AuNPs were synthesized using Ziziphus zizyphus leaf extract and characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. Mice were subjected to a single intraperitoneal injection of AuNPs at a dose of 1 g/mg (grams per milligram) or a daily dose of 1 mg/kg for 28 days. Various parameters, including gold bioaccumulation, survival, behavior, body weight, and blood glucose levels, were measured. Histopathological changes and organ indices were assessed. RESULTS: Gold levels in the blood and heart did not significantly increase with daily administration of AuNPs. However, there were proportional increases in gold content observed in the liver, spleen, and kidney, indicating effective tissue uptake. Histopathological alterations were predominantly observed in the kidney, suggesting potential tissue injury. CONCLUSIONS: The findings of this study indicate that ∼50 nm AuNPs synthesized using Z. zizyphus leaf extract can induce adverse effects, particularly in the kidney, in mice. These results highlight the importance of addressing safety concerns when using AuNPs in medical applications. Further investigations that encompass a comprehensive set of toxicological parameters are necessary to confirm the long-term adverse effects of AuNP exposure.

Synergistic Beneficial Effects of Resveratrol and Diet on High-Fat Diet-Induced Obesity.

Introduction: Despite decades of research, obesity and its related medical complications remain a major health concern globally. Therefore, novel therapeutic strategies are needed to combat obesity and its numerous debilitating complications. Resveratrol (RES) has a potential therapeutic effect in obesity and diabetes by improving oxidative metabolism and insulin signaling. Background and Objectives: The aim of this study was to investigate the effect of RES treatment on weight loss and glucose and fatty acid metabolism. Methods: Obesity was induced in 24 mice by exposure to a high-fat diet (HFD) for 8 weeks. Mice were randomly assigned to one group of either: group 1: control, non-treated low-fat diet (LFD) for 12 weeks (n = 8), group 2: non-treated high-fat diet (HFD) for 12 weeks (n = 8), group 3: RES-treated HFD (HFD + RES) (n = 8), or group 4: RES-treated and switched to LFD (HFD-LFD + RES) (n = 8). HFD + RES mice were first fed an HFD for 8 weeks followed by 4 weeks of RES. The HFD-LFD + RES group was first fed an HFD for 8 weeks and then treated with RES and switched to an LFD for 4 weeks. Results: After 12 weeks, group 2 mice had significantly higher body weights compared to group 1 (23.71 ± 1.95 vs. 47.83 ± 2.27; p < 0.05). Group 4 had a significant decrease in body weight and improvement in glucose tolerance compared to mice in group 2 (71.3 ± 1.17 vs. 46.1 ± 1.82 and 40.9 ± 1.75, respectively; p < 0.05). Skeletal muscles expression of SIRT1, SIRT3, and PGC1α were induced in group 3 and 4 mice compared to group 2 (p < 0.01), with no changes in AMP-activated protein kinase expression levels. Furthermore, combination of RES and diet ameliorated skeletal muscle intermediate lipid accumulation and significantly improved insulin sensitivity and secretion. Conclusions: The results of this study suggest a synergistic beneficial effect of LFD and RES to lower body weight and enhance glucose and fatty acid metabolism.

The Effect of Long-Term Second-Generation Antipsychotics Use on the Metabolic Syndrome Parameters in Jordanian Population.

Objectives: The aim of this study was to determine the incidence of metabolic syndrome in patients treated with second-generation antipsychotics (SGAs). Methods: In this retrospective study, we reviewed patients' electronic medical records (EMRs) of all patients who received one SGA for at least six months, excluding patients who were taking other medications that are associated with significant effect on metabolic syndrome. Relevant clinical information was collected prior to starting the SGA and after six months of continuous use of the same SGA. Results: A total of 91 patients were included in the study. The majority of patients (72%) were diagnosed with schizophrenia. After six months of taking the SGA, 44% of patients experienced elevated systolic pressure, 54.9% had elevated triglyceride, and 31.9% had impaired glucose levels (p value < 0.05). Prior to initiating SGA therapy, 14.3% of patients had metabolic syndrome, while 37.4% had metabolic syndrome after six months of therapy, and it was more prominent in males compared to female patients (p value < 0.05). Conclusion: This study found a strong correlation between SGA use and the appearance of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels. These findings highlight the importance of assessing metabolic deregulations to minimize SGA associated metabolic abnormalities.

Role of CoA and acetyl-CoA in regulating cardiac fatty acid and glucose oxidation.

CoA (coenzyme A) and its derivatives have a critical role in regulating cardiac energy metabolism. This includes a key role as a substrate and product in the energy metabolic pathways, as well as serving as an allosteric regulator of cardiac energy metabolism. In addition, the CoA ester malonyl-CoA has an important role in regulating fatty acid oxidation, secondary to inhibiting CPT (carnitine palmitoyltransferase) 1, a key enzyme involved in mitochondrial fatty acid uptake. Alterations in malonyl-CoA synthesis by ACC (acetyl-CoA carboxylase) and degradation by MCD (malonyl-CoA decarboxylase) are important contributors to the high cardiac fatty acid oxidation rates seen in ischaemic heart disease, heart failure, obesity and diabetes. Additional control of fatty acid oxidation may also occur at the level of acetyl-CoA involvement in acetylation of mitochondrial fatty acid ß-oxidative enzymes. We find that acetylation of the fatty acid ß-oxidative enzymes, LCAD (long-chain acyl-CoA dehydrogenase) and ß-HAD (ß-hydroxyacyl-CoA dehydrogenase) is associated with an increase in activity and fatty acid oxidation in heart from obese mice with heart failure. This is associated with decreased SIRT3 (sirtuin 3) activity, an important mitochondrial deacetylase. In support of this, cardiac SIRT3 deletion increases acetylation of LCAD and ß-HAD, and increases cardiac fatty acid oxidation. Acetylation of MCD is also associated with increased activity, decreases malonyl-CoA levels and an increase in fatty acid oxidation. Combined, these data suggest that malonyl-CoA and acetyl-CoA have an important role in mediating the alterations in fatty acid oxidation seen in heart failure.

Effect of Estrogen and Progesterone Hormones on the Expression of Angiotensin II Receptors in the Heart and Aorta of Male Rats.

BACKGROUND: Activation of the Angiotensin II type 1 receptor (AT1R) has been implicated in the pathogenesis of the cardiovascular disease, while activation of Angiotensin II type 2 receptor (AT2R) leads to effects that are opposite to those mediated by AT1R. The interaction between female sex hormones and the renin-angiotensin system was proven to play an essential role in the pathological changes in the cardiovascular system. OBJECTIVES: To investigate the direct effect of estrogen and progesterone on arterial and cardiac AT1R and AT2R expression in vivo in male. METHOD: Male adult rats were assigned into four groups: Group 1 (control), group 2 (progesterone treated group; 10mg/kg), group 3 (estrogen treated group; 20µg/kg) and group 4 (progesterone; 10mg/kg + estrogen; 20µg/kg treated group). All treatments were administrated subcutaneously every second day for 21days. RESULTS: Estrogen treatments increase the left ventricle (LV) protein expression of AT1R, and progesterone treatment decreased the LV protein expression of AT2R. In the aorta, estrogen treatment increased the mRNA expression levels of AT1R, while progesterone treatment increased the AT2R mRNA expression levels. Estrogen treatment decreases the LV and aortic endothelial nitric-oxide synthase (eNOS) mRNA levels while progesterone treatments decrease the LV eNOS mRNA levels but increase the aortic eNOS mRNA levels. The serum angiotensin II levels were increased by estrogen treatment only. CONCLUSION: Both estrogen and progesterone treatments appear to have a harmful effect on the male rat hearts, possibly by increasing the protein expression of AT1R (for estrogen), decrease the protein and mRNA expression of AT2R (for progesterone), and decrease the eNOS mRNA levels (for both). However, it seems that progesterone but not estrogen exerts a vascular protective effect in males.

Synthesis of Gold Nanoparticles Using Leaf Extract of Ziziphus zizyphus and their Antimicrobial Activity.

(1) Background: There is a growing need for the development of new methods for the synthesis of nanoparticles. The interest in such particles has raised concerns about the environmental safety of their production methods; (2) Objectives: The current methods of nanoparticle production are often expensive and employ chemicals that are potentially harmful to the environment, which calls for the development of "greener" protocols. Herein we describe the synthesis of gold nanoparticles (AuNPs) using plant extracts, which offers an alternative, efficient, inexpensive, and environmentally friendly method to produce well-defined geometries of nanoparticles; (3) Methods: The phytochemicals present in the aqueous leaf extract acted as an effective reducing agent. The generated AuNPs were characterized by Transmission electron microscopy (TEM), Scanning electron microscope (SEM), and Atomic Force microscopy (AFM), X-ray diffraction (XRD), UV-visible spectroscopy, energy dispersive X-ray (EDX), and thermogravimetric analyses (TGA); (4) Results and Conclusions: The prepared nanoparticles were found to be biocompatible and exhibited no antimicrobial or antifungal effect, deeming the particles safe for various applications in nanomedicine. TGA analysis revealed that biomolecules, which were present in the plant extract, capped the nanoparticles and acted as stabilizing agents.

Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox.

Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

Angiotensin 1-7 ameliorates diabetic cardiomyopathy and diastolic dysfunction in db/db mice by reducing lipotoxicity and inflammation.

BACKGROUND: The angiotensin-converting enzyme 2 and angiotensin-(1-7) (Ang 1-7)/MasR (Mas receptor) axis are emerging as a key pathway that can modulate the development of diabetic cardiomyopathy. We studied the effects of Ang 1-7 on diabetic cardiomyopathy in db/db diabetic mice to elucidate the therapeutic effects and mechanism of action. METHODS AND RESULTS: Ang 1-7 was administered to 5-month-old male db/db mice for 28 days via implanted micro-osmotic pumps. Ang 1-7 treatment ameliorated myocardial hypertrophy and fibrosis with normalization of diastolic dysfunction assessed by pressure-volume loop analysis and echocardiography. The functional improvement by Ang 1-7 was accompanied by a reduction in myocardial lipid accumulation and systemic fat mass and inflammation and increased insulin-stimulated myocardial glucose oxidation. Increased myocardial protein kinase C levels and loss of phosphorylation of extracellular signal-regulated kinase 1/2 were prevented by Ang 1-7. Furthermore, Ang 1-7 treatment decreased cardiac triacylglycerol and ceramide levels in db/db mice, concomitantly with an increase in myocardial adipose triglyceride lipase expression. Changes in adipose triglyceride lipase expression correlated with increased SIRT1 (silent mating type information regulation 2 homolog 1) levels and deacetylation of FOXO1 (forkhead box O1). CONCLUSIONS: We identified a novel beneficial effect of Ang 1-7 on diabetic cardiomyopathy that involved a reduction in cardiac hypertrophy and lipotoxicity, adipose inflammation, and an upregulation of adipose triglyceride lipase. Ang 1-7 completely rescued the diastolic dysfunction in the db/db model. Ang 1-7 represents a promising therapy for diabetic cardiomyopathy associated with type 2 diabetes mellitus.