Perivascular adipose tissue (PVAT) regulates vascular tone, and high‐fat diets reportedly lead to the loss of its anti‐contractile properties. Methionine restriction recapitulates many caloric restriction metabolic effects and increases liver expression of activating transcription factor 4 (ATF4) and downstream targets with anti‐contractile properties such as cystathionine‐β‐synthase (CBS) and cystathionine‐γ‐lyase (CSE). We hypothesized that dietary methionine restriction would prevent high‐fat diet‐induced PVAT dysfunction by increasing ATF4 expression. Male Wistar rats were fed control (C, 10% calories from fat) or high‐fat diets (H, 60% calories from fat) (HFD) that were methionine replete (R, 0.86% methionine) or deplete (D, 0.12% methionine) for 12 weeks. Methionine restriction prevented body mass increases, independent of fat content, and had no effect on blood pressure or arterial contraction to norepinephrine (10 μM) or relaxation to acetylcholine (10 μM). In this feeding paradigm, HFD did not induce PVAT dysfunction. CR diet increased ATF4 transcript levels in multiple PVAT depots but did not consistently affect expression of downstream targets. Protein expression of ATF4 and its targets varied largely for all groups. In conclusion, 12 week methionine restriction profoundly affected body mass but not blood pressure or arterial reactivity in the presence or absence of PVAT.

Patients after an acute coronary syndrome (ACS) with preserved left ventricle ejection fraction (LVEF) (n = 45, 10 female) were guided by exercise training for 6 months after percutaneous coronary intervention. Exercise capacity, LVEF, standard resting ECG, and 24‐h Holter recording were measured at baseline. Time and frequency domain heart rate variability were analyzed over 24 h. Sokolow–Lyon index, as a marker of left ventricular hypertrophy and P wave Terminal Force in lead V1 (PTF), a marker of left atrial dilatation, along with the standard parameters were analyzed from ECG. A training load of over 6 months (TRIMP) was calculated. Subjects were categorized according to training responses in exercise capacity as low (−3 ± 4%), average (6 ± 2%), and high (15 ± 6%) responders. PTF and P wave duration at baseline differed between the groups: 0.051 ± 0.018, 0.028 ± 0.023, and 0.016 ± 0.015 ms (p < 0.0001) and 120 ± 11, 113 ± 12 and 104 ± 13 ms (p = 0.002) for low, average, and high groups, respectively. Other ECG variables, or any clinical parameters (e.g., sex, age, baseline fitness, LVEF) at baseline or TRIMP were not associated with the training response. Left atrial dilatation, as indicated by PTF on surface ECG, is associated with a low training response in exercise capacity in patients after ACS.

Portable near‐infrared spectroscopy (NIRS) provides a noninvasive measure of local muscle metabolic demand through muscle oxygen saturation (SmO2). This study aimed to evaluate acute SmO2 responses in exercising and non‐exercising muscles during an isometric test conducted before and after exercise. Twelve physically active men (25 ± 6 years; 1.75 ± 0.07 m) performed three maximal voluntary contractions (MVC) and a 45‐s isometric contraction at 70% MVC (IC70%) before and after completing five sets of 30 concentric knee extensions at 180°·s−1, with 60 s rest between sets, on an isokinetic dynamometer. SmO2 was recorded in the vastus lateralis (exercised and non‐exercised leg) and triceps brachii. Significant differences in SmO2 were observed between exercised and non‐exercised legs both pre‐ (p = 0.048) and post‐exercise (p < 0.001), whereas no significant changes were found in the triceps brachii or non‐exercising vastus lateralis. Acute responses to isometric exercise differed between SmO2 and torque measures. While the torque of the IC70% did not change following the exercise protocol, SmO2 showed a higher deoxygenation response during exercise. The isometric test did not indicate any redistribution of muscle oxygenation from non‐exercising to exercising muscles. These results provide novel insights into the dissociation between mechanical and microvascular responses during isometric exercise and support the potential of this test as a practical tool for monitoring training loads.

Apneas performed during hypoxia cause pronounced bradycardia and cardiac arrhythmias. What remains unclear is the intraindividual consistency of these responses. Therefore, we assessed the within‐day and between‐day repeatability of responses to hypoxic apneas, including the genesis of arrhythmias or electrocardiogram (ECG) changes. Sixteen participants (8F/8M, 25 ± 3 years, BMI 23.7 ± 3.4 kg/m2, mean ± SD) completed four hypoxic apneas per day on consecutive days, time‐matched to a maximal apnea on day 1 (39 ± 16 s). We quantified heart rate (HR) and mean arterial pressure (MAP) repeatability using within‐subject standard deviations (WSSD), [95%CI]. We hypothesized that WSSDs would be <5 bpm and <4 mmHg for HR and MAP. We also assessed the repeatability of arrhythmias or ECG changes. Within‐day, the HR WSSD was 4.4 bpm [3.7, 5.6], and the MAP WSSD was 4.1 mmHg [3.4, 5.1]. Between‐day comparisons had somewhat higher WSSDs: HR was 5.7 bpm [5.0, 6.5] and MAP was 5.0 mmHg [4.4, 5.8]. Arrhythmias or ECG changes occurred during 45% of apneas. These data indicate poor repeatability of electrical conduction changes during apneas. Conversely, our WSSD data indicate good within‐day and between‐day repeatability, albeit somewhat higher than hypothesized. These data therefore indicate that hypoxic apneas are a repeatable laboratory stressor for HR and MAP, but that researchers should exercise caution in interpreting individual‐level arrhythmia data.

Individuals with multiple sclerosis (MS) exhibit reduced physical capacity, partly due to autonomic dysfunction. Autonomic impairments are well documented, but peripheral blood flow regulation during exercise remains unclear. We compared peripheral vascular responses to dynamic handgrip exercise, with and without a mild sympathoexcitatory stimulation, in individuals with and without MS. Twenty‐one individuals with MS (M/F: 4/17; 43 ± 10 yrs) and 27 individuals without MS (M/F: 10/17; 28 ± 6 yrs) completed a 5‐min supine dynamic handgrip exercise at 15% and 30% maximal voluntary contraction, which were repeated during −20 mmHg lower body negative pressure (LBNP). BP was assessed using finger photoplethysmography, and brachial artery blood flow via ultrasound. Individuals with MS had increased forearm vascular conductance to the inactive limb at baseline and in response to exercise compared to controls (Baseline to 30% MVC with LBNP: MS: +32% vs. Non‐MS: −12%; p for interaction <0.05). These changes occurred despite no differences between groups for forearm vascular conductance of the inactive limb (p for interaction = 0.523), and an attenuated increase in MAP in the group with MS during LBNP (p for interaction = 0.024). These findings suggest impaired vasomotor regulation in individuals with MS, particularly in response to combined mild sympathoexcitatory stimuli, compared to individuals without MS.

Doxorubicin treatment of mice represents a convenient model to study the effects of proteinuria on proteolytic processing of the epithelial Na+ channel (ENaC) and urinary Na+ and fluid handling. Prior studies have shown enhanced ENaC γ subunit proteolysis and Na+ and fluid retention in 129S1/SvImJ mice treated with doxorubicin. We examined whether 129S2/SvPas mice could be used to study doxorubicin‐induced proteinuria. 129S2/SvPas mice treated with 18 μg/g doxorubicin exhibited significantly reduced urinary albumin/creatinine compared to that described for 129S1/SvImJ mice. Proteolytic processing of ENaC's γ subunit and sensitivity of urinary Na+ and K+ to the ENaC blocker, benzamil, were not enhanced by doxorubicin. Differences in the DNA repair enzyme, DNA‐activated protein kinase (DNA‐PKcs) may contribute to the difference in doxorubicin susceptibility of 129S2/SvPas and 129S1/SvImJ mice. Sequencing of the Prkdc, encoding DNA‐PKcs, showed that 129S2/SvPas mice lack a polymorphism (Arg2140Cys) that has previously been implicated in doxorubicin sensitivity in 129S1/SvImJ mice. The status of this polymorphism in various experimental mouse strains, and therefore implications for studying doxorubicin‐induced proteinuria, is discussed.

Archaeological and anthropological evidence suggests that human ancestors' diets were rich in fiber, potassium, and complex carbohydrates, while low in sodium, refined sugars, and energy density. Over time, agroindustrialization led to diets poorer in fiber and micronutrients but higher in sodium, simple sugars, and calorie‐dense foods. This shift contributed to the rise of noncommunicable diseases (NCDs) such as obesity, type 2 diabetes, and cardiovascular diseases, which now account for 70% of global premature deaths. Maternal nutrition affects fetal development and long‐term health. High sucrose or fructose intake during pregnancy can alter placental function, impacting fetal growth and metabolism. Placentae from male and female fetuses may respond differently to maternal diet. However, the effects of excessive maternal fructose intake on the placenta and offspring remain underexplored. In this study, rat dams consuming fructose‐sweetened beverages ate less food but drank more, significantly impacting placental volume and vascular structure. Long‐term effects on offspring were sex‐specific: females showed greater water retention and liver fat accumulation. High maternal fructose intake altered placental anatomy and had sex‐specific effects on kidney and liver function in adult offspring, even without further fructose exposure. These findings highlight the importance of maternal diet in preventing future metabolic diseases.

This study aimed to evaluate the acute metabolic effects of oral ketone esters (KE) in individuals with and without metabolic syndrome (MetS) on resting energy expenditure (REE), respiratory exchange ratio (RER), and substrate utilization using respiratory gas exchange. Eight participants with MetS and 8 without MetS matched for age, race, and ethnicity completed a randomized, single‐blind, placebo‐controlled crossover study. Participants underwent a cardiometabolic screening to confirm MetS, followed by two experimental trials. Respiratory gases were measured for 15 min at baseline and 45 and 105 min after a randomly assigned KE or placebo beverage. Following KE ingestion, RER, carbohydrate oxidation (CarbOx), and blood ketones increased significantly, while blood glucose and fat oxidation (FatOx) decreased significantly, irrespective of group. The MetS group showed higher βHB responses to the KE condition than their matched controls, but blood glucose reductions were comparable between groups. Substrate oxidation was similar between the MetS and matched control groups across conditions. Irrespective of MetS status, oral KE acutely increase CarbOx and RER, while concurrently reducing FatOx, without altering REE, suggesting that substrate utilization shifts toward greater CarbOx following KE. Exogenous ketosis may be a promising nonpharmacological strategy to improve metabolic function in individuals with or at risk for MetS.