The present study evaluated the potential beneficial effect of kefir (KF) against fatigue. Furthermore, the composition of the gut microbiota is related to health benefits in the host; therefore, the study also investigated the effect of KF on the gut microbiota composition. Male ICR mice from four groups (= 8 per group) were orally administered KF once daily for four weeks at 0, 2.15, 4.31, and 10.76 g/kg/day and were designated as the vehicle, KF-1X, KF-2X, and KF-5X groups, respectively. The gut microbiota was analyzed using 16S rRNA gene sequencing. The results showed a significant clustering of cecum after treatment in the vehicle, KF-1X, KF-2X, and KF-5X groups. The KF-2X and KF-5X groups showed a decreased/ratio compared with the vehicle group. In addition, anti-fatigue activity and exercise performance were evaluated on the basis of exhaustive swimming time, forelimb grip strength, and levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) after a swimming exercise. The exhaustive swimming time for the KF-1X, KF-2X, and KF-5X groups was significantly longer than that for the vehicle group, and the forelimb grip strength of the KF-1X, KF-2X, and KF-5X groups was also significantly higher than that of the vehicle group. KF supplementation also decreased serum lactate, ammonia, BUN, and CK levels after the swimming test. However, tissue glycogen content, an important energy source for exercise, increased significantly with KF supplementation. Thus, KF supplementation can alter the gut microbiota composition, improve performance, and combat physical fatigue.

Influenza A virus (IAV) infection-associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion ofγδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substratethat bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.

BACKGROUND:Anaplastic thyroid cancer is an aggressive and fatal malignancy. Many advanced cancers are characterized by glucose dependency, leading to oxidative stress and cellular proliferation. Therefore, we sought to determine if a low glucose environment (in vitro) or a ketogenic diet (in vivo) could inhibit anaplastic thyroid cancer tumor growth when combined with the antioxidant N-acetylcysteine.

METHODS:In vivo, nude mice were injected with the anaplastic thyroid cancer cell line 8505C (n = 6/group). Group 1 was fed a standard diet; Group 2 was fed a ketogenic diet; Group 3 was given standard diet with N-acetylcysteine (40 mM in the drinking water); and Group 4 was fed ketogenic diet with N-acetylcysteine. Tumor volumes, ketones, and glucose were measured. H&E stains and immunohistochemistry for Ki-67 and Caspase 3 were performed on the tumors. In vitro, 8505C cells were cultured in high glucose (25 mM), low glucose (3 mM), high glucose plus N-acetylcysteine (200 uM), or low glucose plus N-acetylcysteine for 96 hours. We performed CyQUANT proliferation (Thermo Fisher Scientific, Waltham, MA), Seahorse glycolytic stress (Agilent, Santa Clara, CA), and reactive oxidative stress assays.

RESULTS:Ketogenic diet plus N-acetylcysteine decreased in vivo tumor volume compared to standard diet (22.5 ± 12.4 mmvs 147± 54.4 mm, P<.05) and standard diet plus N-acetylcysteine (P<.05). Blood ketone levels were significantly higher for the mice in the ketogenic diet group compared to standard diet (1.74 mmol/L vs 0.38 mmol/L at week 5, P<.001). However, blood glucose levels were not significantly different between ketogenic diet and standard diet groups. Cells cultured in low glucose plus N-acetylcysteine had significantly reduced proliferation compared to high glucose (98.1± 5.0 relative fluorescence units vs 157.8 ± 2.1 relative fluorescence units, P<.001). Addition of N-acetylcysteine to low glucose lowered glycolysis function compared to high glucose (39.0± 2.2 mpH/min/cell vs 89.1 ± 13.2 mpH/min/cell, P<.001) and high glucose plus N-acetylcysteine (37.4± 2.5 mpH/min/cell vs 70.3 ± 3.3 mpH/min/cell, P<.001). Low glucose plus N-acetylcysteine decreased reactive oxidative stress compared to high glucose (119± 34.7 relative fluorescence units vs 277 ± 16.0 relative fluorescence units, P = .014).

CONCLUSION:The combination of a ketogenic diet or glucose restriction with the antioxidant- N-acetylcysteine significantly reduced tumor growth in vivo and in vitro. Further studies are warranted to explore these metabolic therapies in anaplastic thyroid cancer.

This study investigated the effect of ketogenic diet on monosodium glutamate (MSG)-induced testicular dysfunction. Forty-six male rats (180 ± 40 g) were grouped into two groups (23 rats each); control group and MSG-induced group (4 mg/kg bw) for 28 days. At the 29th day, 5 rats from both group were sacrificed to establish testicular dysfunction. The remaining animals from the control group was further divided into three sub-groups and treated for 42 days; untreated group, ketogenic diet only and curcumin only as the standard drug (150 mg/kg bw). In the pre-treatment, the administration of MSG resulted in a significant (p < 0.05) decrease in the testis-body weight ratio, alkaline phosphatase (ALP), acetylcholine esterase (AChE), cholesterol, triglycerides (TG), nitric oxide (NO), glycogen, protein and antioxidant enzymes in the testis. In the post treatment, the MSG only group significantly reduced testicular cholesterol, catalase (CAT) and NO. In contrast, MSG + ketogenic diet group showed a significant increase in levels of rat testicular acid phosphatase (ACP), ALP, cholesterol, HMG-CoA, TG, malondialdehyde (MDA), reduced glutathione (GSH) and NO. The ketogenic diet showed a significant increase (p < 0.05) in the levels of NO, ALP, cholesterol, HMG CoA reductase and (TG). In addition, significant increases in levels of rat testicular ACP, ALP, HMG-CoA, (CAT), SOD and GSH were recorded for MSG + Curcumin group. Taken together, the findings support the prospects of ketogenic diet to enhancethe testicular function in rats.

Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.

BACKGROUND:Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile.

FINDINGS:Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals.

CONCLUSIONS:Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.

SCOPE:Recent findings indicate that ketogenic diet is neuroprotective and electrical stimulation can improve functional recovery from peripheral nerve injury. However, it is not clear whether ketogenic diet and electrical stimulation play synergistical role in the peripheral nerve recovery following injury.

METHODS AND RESULTS:We used ketogenic diet consisting of 3:1 ratio of fat to carbohydrate+protein and coupled it with electrical stimulation treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery was evaluated by electromyography, and axonal regeneration and myelination by histological methods. We also investigated the effects on IGF-1 and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury. Combination of ketogenic diet and electrical stimulation synergistically increased muscle force in biceps femoris and gluteus maximus and prevented development of hypersensitivity in biceps femoris. It promoted peripheral nerve regeneration by increasing total axons, axons density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects were due to modulation of IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue.

CONCLUSION:Our results establish that ketogenic diet and electrical stimulation promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach. This article is protected by copyright. All rights reserved.

Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects.

Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells.Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.

The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5weeks of age. Beginning at 8weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.

The aim of this study is to investigate the effect of ketogenic metabolism, induced by different diet interventions, on histone acetylation and its potential antioxidant capacity to injured spinal cord tissue in rats. 72 male Sprague-Dawley rats were randomly divided into 4 groups, fed with ketogenic diet (KD), every other day fasting (EODF), every other day ketogenic diet (EODKD) and standard diet (SD) respectively for 2 weeks.β-Hydroxybutyrate (βOHB) concentration was measured both in serum and cerebrospinal fluid (CSF). C5 spinal cord tissue was harvested before, at 3 h and 24 h after injury for analysis of HDAC activity, histone acetylation and oxidative makers. All three dietary interventions resulted in a significant increase of βOHB level in both serum and CSF, and inhibited HDAC activity by 31-43% in spinal cord. Moreover, the expressions of acetylated histone AcH3K9 and AcH3K14 were significantly increased. Anti-oxidative stress genes Foxo3a and Mt2 and related proteins, such as mitochondrial superoxide dismutase (SOD), FOXO3a, catalase were increased in dietary intervention groups. After SCI, high ketogenic metabolism demonstrated significant reduction of the expression of lipid peroxidation factors malondialdehyde (MDA), and this might contribute to the reported neuroprotection of the spinal cord from oxidative damage possibly mediated by increasing SOD. The result of this study suggested that by inhibiting HDAC activity and modifying related gene transcription, ketogenic metabolism, induced by KD, EODF or EODKD, might reduce oxidative damage in the spinal cord tissue after acute injury.

The syndrome of heart failure (HF) promotes central and peripheral dysfunctions that result in functional capacity decrease, leading to fatigue, dyspnea, and exercise intolerance. The use of light-emitting diode therapy (LEDT) has shown good results reducing fatigue and exercise intolerance, when applied on skeletal muscles before or after exercises. Thereby, the aim of this study was to compare the effects of LEDT on functional capacity, aerobic power, and hemodynamic function in HF rats. Male Wistar rats (230-260 g) were randomly allocated into three experimental groups: Sham (n = 6), Control-HF (n = 4), and LEDT-HF (n = 6). The animals were subjected to an exercise performance test (ET) with gas analysis coupled in a metabolic chamber for rats performed two times (6 and 14 weeks after myocardial infarction). On the day after the baseline aerobic capacity test, the animals were submitted during 8 weeks to the phototherapy protocol, five times/week, 60 s of irradiation, 6 J delivered per muscle group. Statistical analysis was performed by one- and two-way ANOVAs with repeated measuresand Student-Newman-Keuls post hoc tests (p ≤ 0.05). Comparing the percentage difference (Δ) between baseline and the final ET, there was no significant difference for the VO2max variable considering all groups. However, Sham and LEDT-HF groups showed higher relative values than the Control-HFgroup, respectively, for distance covered (27.7 and 32.5 %), time of exercise test (17.7 and 20.5 %), and speed (13.6 and 12.2 %). In conclusion, LEDT was able to increase the functional capacity evaluated by distance covered, time, and speed of exercise in rats with HF.

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance.

Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer's disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role ofβ-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expressionlevels of β-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P<0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation ofβ-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P>0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.

Background:Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder affecting 7-10 million individuals. The pathologic hallmark of PD is nigrostriatal dopaminergic neuron loss, leading to several motor and nonmotor disturbances, such as akinesia, gait disturbance, depression, and anxiety. Recent animal studies have demonstrated that physical exercise improves behavioral and neuropathological deficits in PD. However, the exact underlying mechanism underlying this effect remains unclear. In this study, we investigated whether long-term exercise has neuroprotective effects on dopaminergic nigrostriatal neurons and whether it further alleviates impairment of the gait pattern, locomotor activity, akinesia, and anxiety-like behavior in PD rats.

Methods:A hemiparkinsonian rat model, generated by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to evaluate neuroprotective effects and motor behaviors. Comprehensive spatiotemporal gait analysis, open-field locomotor activity, akinesia, apomorphine-induced rotational analysis, and dopaminergic neuron degeneration level were assessed every week and up to 8 weeks after daily voluntary running wheel exercise.

Results:Compared with the sham-treated group, we found that 10 weeks of voluntary exercise (i.e., 2-week exercise before PD lesion and 8-week exercise post-PD lesion) significantly reduced 6-OHDA-induced motor deficits in the gait pattern, akinesia, and rotational behavior in the exercise group. Immunohistochemically, a tyrosine hydroxylase-positive neuron in the substantia nigra was significantly preserved in the exercise group.

Conclusions:Our results demonstrated that long-term exercise training is effective for neuroprotection and further attenuates motor declines induced by 6-OHDA in an experimental model of PD. Our data further highlighted potential therapeutic effects of long-term physical exercise relevant to clinical effects for further potential application on human PD subjects.

The cardio-protective effects of a low carbohydrate ketogenic diet following global ischaemic injury as compared to rats fed a normal and high carbohydrate diet for a period of 19 weeks, were investigated. The reperfusion recovery of coronary flow was highly significant in the low carbohydrate ketogenic diet group. Although the initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups, after 15 minutes, the momentum for faster recovery was maintained in the low carbohydrate ketogenic diet group. Ultrastructural observations of the cardiac muscles have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group.This study demonstrates that a low carbohydrate ketogenic diet is cardio-protective functionally.

INTRODUCTION: Ischaemia and reperfusion lead to cell death. These pathways are regulated and hence are subjected to therapeutic intervention. Previously, we have shown that a low carbohydrate ketogenic diet (LCKD) reduces the risk factors for heart disease in obese patients. This study is aimed at understanding the cardio-protective effects of LCKD following global ischaemic injury in rats.

MATERIALS AND METHODS: Rats weighing 190-250 g were divided into normal diet (ND), LCKD and high carbohydrate diet (HCD) groups consisting of six animals in each group. Specific diets were given to each group for a period of 19 weeks. Changes in body weight, ultrastructure of the cardiac muscles and the cardio-protective effects of the LCKD group as compared to the ND and HCD groups were investigated in rats following global ischaemic injury.

RESULTS: Electron microscopic studies have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. Rats on LCKD had a remarkable tolerance to ischaemia and a faster recovery of cardiac function following reperfusion. The initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups. However, after 15 minutes, the momentum for faster recovery was significantly maintained in the LCKD group (P < 0.05). The reperfusion recovery of coronary flow was highly significant (P < 0.05) in the LCKD regime. The increase in left ventricle end diastolic pressure, coronary vascular resistance and the changes in body weight were not significant between the experimental groups.

DISCUSSION AND CONCLUSION: This is a unique study showing ultrastructural variation in cardiac muscle in relation to cardio-protective function in rats fed a low carbohydrate ketogenic diet. This study suggests that the LCKD is cardio-protective functionally.The underlying mechanism of the cardio-protective effect of an LCKD needs to be elucidated.

Human and animal studies strongly suggest that dietary gluten could play a causal role in the etiopathogenesis of type 1 diabetes (T1D). However, the mechanisms have not been elucidated. Recent reports indicate that the intestinal microbiome has a major influence on the incidence of T1D. Since diet is known to shape the composition of the intestinal microbiome, we investigated using non-obese diabetic (NOD) mice whether changes in the intestinal microbiome could be attributed to the pro- and anti-diabetogenic effects of gluten-containing and gluten-free diets, respectively. NOD mice were raised on gluten-containing chows (GCC) or gluten-free chows (GFC). The incidence of diabetes was determined by monitoring blood glucose levels biweekly using a glucometer. Intestinal microbiome composition was analyzed by sequencing 16S rRNA amplicons derived from fecal samples. First of all, GCC-fed NOD mice had the expected high incidence of hyperglycemia whereas NOD mice fed with a GFC had significantly reduced incidence of hyperglycemia. Secondly, when the fecal microbiomes were compared, Bifidobacterium, Tannerella, and Barnesiella species were increased (p = 0.03, 0.02, and 0.02, respectively) in the microbiome of GCC mice, where as Akkermansia species was increased (p = 0.02) in the intestinal microbiomes of NOD mice fed GFC. Thirdly, both of the gluten-free chows that were evaluated, either egg white based (EW-GFC) or casein based (C-GFC),significantly reduced the incidence of hyperglycemia. Interestingly, the gut microbiome from EW-GFC mice was similar to C-GFC mice. Finally, adding back gluten to the gluten-free diet reversed its anti-diabetogenic effect, reduced Akkermansia species and increased Bifidobacterium, Tannerella, and Barnesiella suggesting that the presence of gluten is directly responsible for the pro-diabetogenic effects of diets and it determines the gut microflora. Our novel study thus suggests that dietary gluten could modulate the incidence of T1D by changing the gut microbiome.

The cornerstone to treat metabolic syndrome and insulin resistance is dietary intervention. Both low-carbohydrate diet (LCD) and low-fat diet (LFD) have been reported to induce weight loss and improve these conditions. One of the factors associated with a subject's adherence to the diet is satiety. The aim of this study was to evaluate the effects of LCD and LFD on body weight, appetite hormones, and insulin resistance. Twenty guinea pigs were randomly assigned to LCD or LFD (60%:10%:30% or 20%:55%:25% of energy from fat/carbohydrate/protein, respectively) for 12 weeks. Weight and food intake were recorded every week. After this period, animals were killed and plasma was obtained to measure plasma glucose and insulin, appetite hormones, and ketone bodies. Guinea pigs fed LCD gained more weight than those fed LFD. The daily amount of food intake in grams was not different between groups, suggesting that food density and gastric distension played a role in satiety. There was no difference in leptin levels, which excludes the hypothesis of leptin resistance in the LCD group. However, plasma glucagon-like peptide-1 was 47.1% lower in animals fed LCD (P<.05). Plasma glucose, plasma insulin, and insulin sensitivity were not different between groups. However, the heavier animals that were fed LFD had impairment in insulin sensitivity, which was not observed in those fed LCD. These findings suggest that satiety was dependent on the amount of food ingested. The weight gain in animals fed LCD may be related to their greater caloric intake, lower levels of glucagon-like peptide-1, and higher protein consumption. The adoption of LCD promotes a unique metabolic state that prevents insulin resistance, even in guinea pigs that gained more weight. The association between weight gain and insulin resistance seems to be dependent on high carbohydrate intake.

INTRODUCTION:Moderate-intensity aerobic exercise has been noted to improve wound healing rates in mice and people, but different intensities of exercise may have different impacts on healing rates. It is important to determine the most beneficial exercise intensity for improving wound healing in people with type 2 diabetes to help prevent wounds from becoming chronic, greatly reduce pain and immobility, and lower the high cost of health care associated with treatment.

OBJECTIVE:The purpose of this study is to determine the impact of low-intensity exercise compared with high-intensity exercise in terms of the rate of wound healing in diabetic mice.

MATERIALS AND METHODS:Twenty-one 10-week-old female diabetic mice were randomly assigned to a sedentary control group (CON), low-intensity treadmill exercise (LEX) group, or high-intensity treadmill exercise (HEX) group. Mice were exercised for 30 minutes, 5 days per week, for 3 weeks. Mice were wounded on their upper back with a 3.5-mm punch biopsy instrument, and wounds were photographed at the same time every day.

RESULTS:In terms of the length of time it took wounds to fully heal, CON mice healed in an average of 14.4± 2.4 days (number of days to decrease to less than 10% of their original size ± standard deviation) and HEX mice in 14.0 ± 3.0 days (P = .396). However, LEX mice healed faster than CON in an average of 10.1 ± 2.3 days (P = .004).

CONCLUSIONS:In this preliminary investigation, low-intensity exercise accelerated wound healing rates in diabetic mice but high-intensity exercise did not. Future studies should investigate the mechanisms behind this effect and evaluate different intensities of exercise on wound healing in humans with type 2 diabetes.

BACKGROUND AND OBJECTIVE:Low-level laser therapy (LLLT) and cryotherapy are widely used treatments in the acute phase of tendon injury. The aim of this study was to investigate the interaction of these two treatments on tendon inflammation and mechanical properties.

MATERIALS AND METHODS:Six groups of six Wistar rats were used in this study. The Achilles tendons of the healthy control group were not subjected to injury or treatment. The tendons of the injured nontreated group (ING) were injured, but not treated. The remaining four groups were injured and subjected to LLLT, cryotherapy, LLLT first/cryotherapy, or cryotherapy first/LLLT. All treatments were performed at 1 h post-trauma. Inflammatory mediators, tendon histology, and biomechanical properties were assessed at 24 h post-trauma by comparing the treatment groups with the ING.

RESULTS:In all treatment groups, the inflammatory process shifted in an anti-inflammatory direction compared with the ING. Significant alterations in cytokine expression were found in only the LLLT group (↓IL-1β) and the combined intervention groups (↓IL-1β, ↓TNF-α, ↑IL-6). It was also found that cryotherapy followed by LLLT was the only treatment that significantly (p < 0.05) improved the biomechanical parameters of force (N) and displacement (mm) at the tendon rupture and corresponded with the best histological scores of all of the treatment groups.

CONCLUSIONS:Our results demonstrate that cryotherapy in combination with LLLT can produce an anti-inflammatory"add-on"effect. The order of therapy administration seems essential, as superior histology and biomechanical results were found in the cryotherapy first/LLLT group.