In Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

Individuals with abdominal obesity and metabolic syndrome (MetS) have augmented risk of all-cause mortality. Lifestyle interventions are effective to treat MetS, however, there are periods during the year in which exercise programs are discontinued and improper dietary habits reappear (e.g., Christmas holidays). We aimed to analyze if exercise-training during Christmas holidays would avoid body-weight gains and cardiometabolic deterioration in MetS individuals, using a randomized control trial. Thirty-eight men with MetS undergoing exercise training were randomly allocated to either continue (TRAIN group, n = 16) or discontinue (HOLID group, n = 22) training, during the three weeks of Christmas. Anthropometrics (body weight, fat, and waist circumference), fasting blood metabolites (glucose, insulin, triglycerides, and cholesterol concentrations) and exercise maximal fat oxidation (FOMAX) and oxygen uptake (VO2PEAK) were determined before and after Christmas. Both groups were similar at baseline in all parameters (p > 0.05). HOLID group increased body weight (91.3 ± 13.0 to 92.0 ± 13.4 kg, p = 0.004), mean arterial pressure (94.0 ± 10.6 to 97.1 ± 8.9 mmHg, p = 0.026), blood insulin (10.2 ± 3.8 to 12.5 ± 5.4 µIU·mL−1, p = 0.003) and HOMA (3.2 ± 1.3 to 4.1 ± 2.3, p = 0.003). In contrast, TRAIN prevented those disarrangements and reduced total (170.6 ± 30.6 to 161.3 ± 31.3 mg·dL−1, p = 0.026) and low-density lipoprotein cholesterol (i.e., LDL-C, 104.8 ± 26.1 to 95.6 ± 21.7 mg·dL−1, p = 0.013). TRAIN also prevented the reductions in exercise FOMAX and VO2PEAK that was observed in the HOLID group (p = 0.002). In conclusion, exercise training during Christmas, prevents body weight gains and the associated cardiovascular (increase in blood pressure and LDL-C) and metabolic (reduced insulin sensitivity) health risks are an optimal non-pharmacological therapy for that period of the year.

Aims To determine if the combination of exercise and statin could normalize postprandial triglyceridaemia (PPTG) in hypercholesteraemic individuals. Methods Eight hypercholesteraemic (blood cholesterol 182 ± 38 mg dL−1; low‐density lipoprotein–cholesterol [LDL‐c] 102 ± 32 mg dL−1) overweight (body mass index 30 ± 4 kg m−2) individuals with metabolic syndrome (MetS) were compared to a group of 8 metabolically healthy (MetH) controls (blood cholesterol 149 ± 23 mg dL−1; LDL‐c 77 ± 23 mg dL−1, and body mass index 23 ± 2 kg m−2). Each group underwent 2 PPTG tests, either 14 hours after a bout of intense exercise or without previous exercise. Additionally, MetS individuals were tested 96 hours after withdrawal of their habitual statin medication to study medication effects. Results A bout of exercise before the test meal did not reduce PPTG in MetS (P = .347), but reduced PPTG by 46% in MetH (413 ± 267 to 224 ± 142 mg dL−1 for 5 h incremental area under the curve; P = .02). In both trials (i.e., either after a bout of intense exercise or without previous exercise), statin withdrawal in MetS greatly increased PPTG (average 65%; P < .01), mean LDL‐c (average 25%; P < .01), total cholesterol (average 16%; P < .01) and apolipoprotein (Apo) B48 (24%; P < .01), without interference from exercise. However, Apo B100 was not affected by statin withdrawal. Conclusion Hypercholesteraemic MetS individuals (compared to MetH controls) fail to show an effect of exercise on reducing PPTG. However, chronic statin medication blunts the elevations in triglyceride after a fat meal (i.e., incremental area under the curve of PPTG) reducing their cardiovascular risk associated with their atherogenic dyslipidaemia. Statin decreases PPTG by reducing the secretion or accelerating the catabolism of intestinal Apo B48.

Pharmacological and non‐pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (ie, metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (ie, exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, 36 hypertensive individuals with metabolic syndrome (MetS) under long‐term prescription with AHM targeting the renin‐angiotensin‐aldosterone system (RAAS) were recruited. Before and after 4 months of high‐intensity interval training (HIIT), participants completed two trials in a double‐blind, randomized order: (a) placebo trial consisting of AHM withdrawal for 3 days and (b) AHM trial where individuals held their habitual dose of AHM. In each trial, 24‐h mean arterial pressure (MAP) was monitored and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin‐to‐creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24‐h MAP (−5.7 mmHg, p < 0.001 and −2.3 mmHg, p = 0.007, respectively). However, there was not interaction between AHM and HIIT on 24‐h MAP (p = 0.240). There was a main effect of AHM increasing PRA (p < 0.001) but no effect on plasma aldosterone concentration (p = 0.368). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.

We sought to determine the effects of substituting parts of aerobic training (AT) by resistance training (RT) on metabolic syndrome (MetS) factors. MetS patients (56±7 years old; BMI 33±5 kg·m-2 and 3.9±0.8 MetS factors) were randomized to undergo one of the following isocaloric, 16-week long exercise programs: i) cycling 4 bouts of 4-min at 90% of HRmax followed by 3 sets of 12 repetitions of 3 lower limb free-weight exercises (HIIT+RT group; n=33), ii) cycling 5 bouts of 4-min at 90% of HRmax (HIIT+HIIT group; n=33) or iii) no exercise control group (CONT group; n=21). We measured the evolution of all five MetS components (Z-score), cardiorespiratory fitness (VO2max), leg strength and power (leg press 1RM and countermovement jump (CMJ)), fasting blood glucose (FG), insulin (FI) and insulin resistance (HOMA2). Both training groups improved VO2max similarly (170±310 and 190±210 mLO2·min-1; P<0.001) and Z-score (-0.12±0.29 and -0.12±0.31 for HIIT+RT and HIIT+HIIT, respectively; P<0.02). However, only HIIT+RT improved CMJ (P=0.002) and leg press 1RM above the HIIT+HIIT group (21% vs 6%; P<0.001). Furthermore, FG only decreased in the HIIT+RT group (5%; P=0.026, time x group). Our findings suggest that substitution of part of HIIT by leg RT, improves glucose control in MetS individuals. Bullets Points: •Most studies addressing the efficacy of endurance vs resistance training are not matched by energy expenditure. •We found that substituting 20% of aerobic training with resistance training reduces hyperglycemia in MetS individuals. •Thus, training recommendations to regain glycemic control in MetS individuals should include resistance training.