Ginger and avocado as nutraceuticals for obesity and its comorbidities.

Obesity is a worldwide epidemic and is one of the factors involved in the etiology of type 2 diabetes mellitus. Obesity induces low-grade inflammation and oxidative stress. The treatment for obesity involves changes in diet, physical activity, and even medication and surgery. Currently, the use of nutraceutical compounds is associated with health benefits. Ginger and avocado are used for many people all around the world; however, its effect as a nutraceutical compound is less known by the general population. For this reason, we searched information of the literature to point its effects on distinct mechanisms of defense against the obesity its comorbidities. The present review aimed showing that these nutraceuticals may be useful in obesity treatment. Reports have shown that ginger and avocado induce antioxidant and anti-inflammatory effects by improving enzymatic activity and modulating obesity-related impairments in the anti-inflammatory system in different tissues, without side effects. Furthermore, ginger and avocado were found to be effective in reversing the harmful effects of obesity on blood lipids. In conclusion, on the basis of the positive effects of ginger and avocado in in vitro, animal, and human studies, these nutraceuticals may be useful in obesity treatment.

Effect of Low-Power Laser (LPL) and Light-Emitting Diode (LED) on Inflammatory Response in Burn Wound Healing.

The aim of the study was to investigate the biochemical and molecular changes in the process of epidermal healing of burn injuries after therapeutic treatment with low-power laser (LPL) and light-emitting diode (LED). Rats were divided into six groups: skin without injury (Sham), burn wounds (BWs), BW + 660-nm LPL, BW + 904-nm LPL, BW + 632-nm LED, and BW + 850-nm LED. The burn wound model was performed using a 100 °C copper plate, with 10 s of contact in the skin. The irradiations started 24 h after the lesion and were performed daily for 7 days. The burn wound groups showed an increase in the superoxide production, dichlorofluorescein, nitrites, and high protein oxidative damage. The activities of glutathione peroxidase and catalase were also increased, and a significant reduction in glutathione levels was observed compared to the control group. However, treatments with 660-nm LPL and 850-nm LED promoted protection against to oxidative stress, and similar results were also observed in the IL-6 and pERK1/2 expression. Taken together, these results suggest that LPL 660 nm and LED 850 nm appear reduced in the inflammatory response and oxidative stress parameters, thus decreasing dermal necrosis and increasing granulation tissue formation, in fact accelerating the repair of burn wounds.

Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition.

The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type.

The role of continuous versus fractionated physical training on muscle oxidative stress parameters and calcium-handling proteins in aged rats.

Age-associated decline in skeletal muscle mass and strength is associated with oxidative stress and Ca(2+) homeostasis disturbance. Exercise should be considered a viable modality to combat aging of skeletal muscle. This study aimed to investigate whether continuous and fractionated training could be useful tools to attenuate oxidative damage and retain calcium-handling proteins. We conducted the study using 24-month-old male Wistar rats, divided into control, continuous, and fractionated groups. Animals ran at 13 m min(-1) for five consecutive days (except weekends) for 6 weeks, for a total period of 42 days. Each session comprised 45 min of exercise, either continuous or divided into three daily sessions of 15 min each. Metabolic and oxidative stress markers, protein levels of mitochondrial transcription factors, and calcium-handling proteins were analyzed. Continuous exercise resulted in reduced ROS production as well as showed a decrease in TBARS levels and carbonyl content. On the other hand, fractionated training increased the antioxidant enzyme activities. The ryanodine receptor and phospholamban protein were regulated by continuous training while sodium calcium exchange protein was increased by the fractionated training. These data suggest that intracellular Ca(2+) can be modulated by various training stimuli. In addition, the modulation of oxidative stress by continuous and fractionated training may play an important regulatory role in the muscular contraction mechanism of aged rats, due to changes in calcium metabolism.

Excessive eccentric exercise-induced overtraining model leads to endoplasmic reticulum stress in mice skeletal muscles.

AIMS: The present study verified the responses of selected endoplasmic reticulum (ER) stress proteins (i.e., BiP, ATF-6, pIRE1, pPERK, and peIF2alpha) in mice skeletal muscles after three different running overtraining (OT) protocols with same external load (i.e., intensity vs. volume), but performed in downhill, uphill and without inclination. MATERIALS AND METHODS: The rodents were randomly divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. The incremental load test and exhaustive test were used as performance parameters. Forty hours after the exhaustive test performed at the end of the OT protocols (i.e., at the end of week 8) and after a 2-week total recovery period (i.e., at the end of week 10), the extensor digitorum longus (EDL) and soleus muscles were removed and used for immunoblotting. KEY FINDINGS: For both skeletal muscle types, the OTR/down protocol increased the pIRE-1, pPERK and peIF2alpha, which were not normalized after the total recovery period. At the end of week 8, the other two OT protocols up-regulated the BiP, pPERK and peIF2alpha levels only for the soleus muscle. These ER stress proteins were not normalized after the total recovery period for the OTR/up group. SIGNIFICANCE: The above findings suggest that the OTR/down protocol-induced skeletal muscle ER stress may be linked to a pathological condition in EDL and soleus muscles.

Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson's Disease.

This study aimed to evaluate the effects of two different protocols for physical exercise (strength and aerobic training) on mitochondrial and inflammatory parameters in the 6-OHDA experimental model of Parkinson's disease. Six experimental groups were used (n = 12 per group): untrained + vehicle (Sham), strength training + vehicle (STR), treadmill training + vehicle (TTR), untrained + 6-OHDA (U + 6-OHDA), strength training + 6-OHDA (STR + 6-OHDA), and treadmill training + 6-OHDA (TTR + 6-OHDA). The mice were subjected to strength or treadmill training for 8 weeks. PD was induced via striatal injection of 6-OHDA 24 h after the last exercise session. Mice were euthanized by cervical dislocation and the striatum and hippocampus were homogenized to determine levels of tyrosine hydroxylase (TH), nuclear factor kappa B (NF-κB) p65, and sirtuin 1 (Sirt1) by western blot; tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-17, interferon-γ (IFN-γ), and transforming growth factor ß1 (TGF-ß1) levels by ELISA; NO content; and complex I (CI) activity. STR + 6-OHDA mice had higher TH levels and CI activity and lower NF-κB p65 and IFN-γ levels in the striatum compared to U + 6-OHDA mice, while TTR + 6-OHDA mice had higher Sirt1 levels and CI activity in both the striatum and the hippocampus, compared to U + 6-OHDA mice. Strength training increased CI activity and TH and Sirt1 levels and reduced NO, NF-κB p65, TNF-α, IFN-γ, IL-1ß, and TGF-ß1 levels in 6-OHDA mice, while treadmill exercise increased CI activity and NO, TH, and Sirt1 levels and reduced NF-κB p65, TNF-α, IFN-γ, and IL-1ß levels. Our results demonstrated that both treadmill training and strength training promote neuroprotection, possibly by stimulating Sirt1 activity, which may in turn regulate both mitochondrial function and neuroinflammation via deacetylation of NF-κB p65. Changes in nitric oxide levels may also be a mechanism by which 6-OHDA-induced inflammation is controlled.

Downhill Running-Based Overtraining Protocol Improves Hepatic Insulin Signaling Pathway without Concomitant Decrease of Inflammatory Proteins.

The purpose of this study was to verify the effects of overtraining (OT) on insulin, inflammatory and gluconeogenesis signaling pathways in the livers of mice. Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). Rotarod, incremental load, exhaustive and grip force tests were used to evaluate performance. Thirty-six hours after a grip force test, the livers were extracted for subsequent protein analyses. The phosphorylation of insulin receptor beta (pIRbeta), glycogen synthase kinase 3 beta (pGSK3beta) and forkhead box O1 (pFoxo1) increased in OTR/down versus CT. pGSK3beta was higher in OTR/up versus CT, and pFoxo1 was higher in OTR/up and OTR versus CT. Phosphorylation of protein kinase B (pAkt) and insulin receptor substrate 1 (pIRS-1) were higher in OTR/up versus CT and OTR/down. The phosphorylation of IκB kinase alpha and beta (pIKKalpha/beta) was higher in all OT protocols versus CT, and the phosphorylation of stress-activated protein kinases/Jun amino-terminal kinases (pSAPK-JNK) was higher in OTR/down versus CT. Protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) and hepatocyte nuclear factor 4alpha (HNF-4alpha) were higher in OTR versus CT. In summary, OTR/down improved the major proteins of insulin signaling pathway but up-regulated TRB3, an Akt inhibitor, and its association with Akt.

Effects of phonophoresis and gold nanoparticles in experimental model of muscle overuse: role of oxidative stress.

The aim of the study described here was to investigate the effects of pulsed ultrasound and gold nanoparticles (AuNPs) on behavioral, inflammatory and oxidative stress parameters in an experimental model of overuse. Wistar rats performed 21 d of exercise on a treadmill at different intensities and were exposed to ultrasound in the presence or absence of AuNPs. The overuse model promoted behavioral changes and increased creatine kinase, superoxide dismutase and glutathione peroxidase activity, as well as the levels of superoxide, nitrotyrosine, nitric oxide, thiobarbituric acid reactive substance, carbonyl, tumor necrosis factor α and interleukin-6. These values were significantly decreased by AuNPs and by AuNPs plus ultrasound. Catalase activity remained unchanged and the glutathione level increased significantly after exposure to AuNPs plus ultrasound. These results suggest a susceptibility to anxiety as well as elevated levels of oxidative stress. However, therapeutic interventions with AuNPs plus ultrasound reduced the production of oxidants and oxidative damage and improved the anti-oxidant defense system.

Hypothalamic S1P/S1PR1 axis controls energy homeostasis.

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

Atypical transforming growth factor-ß signaling in the hypothalamus is linked to diabetes.

Aging and a high-fat diet are predisposing factors for type 2 diabetes. A study in mice suggests that dietary fat and aging lead to atypical transforming growth factor-ß1 signaling in the hypothalamus, which disturbs whole-body glucose regulation.

Treadmill training increases SIRT-1 and PGC-1 α protein levels and AMPK phosphorylation in quadriceps of middle-aged rats in an intensity-dependent manner.

The present study investigated the effects of running at 0.8 or 1.2 km/h on inflammatory proteins (i.e., protein levels of TNF- α , IL-1 ß , and NF- κ B) and metabolic proteins (i.e., protein levels of SIRT-1 and PGC-1 α , and AMPK phosphorylation) in quadriceps of rats. Male Wistar rats at 3 (young) and 18 months (middle-aged rats) of age were divided into nonexercised (NE) and exercised at 0.8 or 1.2 km/h. The rats were trained on treadmill, 50 min per day, 5 days per week, during 8 weeks. Forty-eight hours after the last training session, muscles were removed, homogenized, and analyzed using biochemical and western blot techniques. Our results showed that: (a) running at 0.8 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with NE rats; (b) these responses were lower for the inflammatory proteins and higher for the metabolic proteins in young rats compared with middle-aged rats; (c) running at 1.2 km/h decreased the inflammatory proteins and increased the metabolic proteins compared with 0.8 km/h; (d) these responses were similar between young and middle-aged rats when trained at 1.2 km. In summary, the age-related increases in inflammatory proteins, and the age-related declines in metabolic proteins can be reversed and largely improved by treadmill training.

Effects of taurine supplementation following eccentric exercise in young adults.

The purpose of the present study was to investigate the effects of taurine supplementation on muscle performance, oxidative stress, and inflammation response after eccentric exercise (EE) in males. Twenty-one participants (mean age, 21 ± 6 years; weight, 78.2 ± 5 kg; height, 176 ± 7 cm) were selected and randomly divided into two groups: placebo (n = 10) and taurine (n = 11). Fourteen days after starting supplementation, subjects performed EE (3 sets until exhaustion, with EE of the elbow flexors on the Scott bench, 80% 1 repetition maximum (RM)). Blood samples were collected and muscle performance was measured on days 1, 14, 16, 18, and 21 after starting the supplements. Then, performance, muscle damage, oxidative stress, and inflammatory markers were analyzed. The taurine supplementation resulted in increased strength levels and thiol total content and decreased muscle soreness, lactate dehydrogenase level, creatine kinase activity, and oxidative damage (xylenol and protein carbonyl). Antioxidant enzymes (superoxide dismutase, catalase, and gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, interleukin-1ß (IL-1ß), and interleukin-10 (IL-10)) were not altered during the recovery period compared with the placebo group. The results suggest that taurine supplementation represents an important factor in improving performance and decreasing muscle damage and oxidative stress but does not decrease the inflammatory response after EE.

Eccentric exercise leads to performance decrease and insulin signaling impairment.

PURPOSE: This study aimed to evaluate the effects of an overtraining (OT) protocol based on eccentric exercise (EE) sessions on the insulin and inflammatory signaling pathways in the skeletal muscles of Swiss mice. METHODS: Rodents were divided into control (C; sedentary mice), trained (TR; performed the aerobic training protocol), and overtrained (OTR; performed the OT protocol). The incremental load test and exhaustive test were used to measure performances before and after exercise protocols. Twenty-four hours after the exhaustive test performed at the end of week 8, the extensor digitorum longus (EDL) and soleus muscles were removed for subsequent protein analysis by immunoblotting. RESULTS: The phosphorylation of insulin receptor beta (pIRbeta; Tyr1146) diminished for EDL and soleus muscles in OTR compared with C. The phosphorylation of insulin receptor substrate 1 (pIRS-1; Ser307) increased for EDL and soleus muscles in OTR compared with C and TR. The phosphorylation of protein kinase B (pAkt; Ser473) diminished for EDL and soleus muscles in OTR compared with C and TR. The phosphorylation of IκB kinase alpha and beta (pIKKalpha/beta; Ser176/180), stress-activated protein kinases/Jun amino-terminal kinases (pSAPK/JNK; Thr183/Tyr185), and the protein levels of suppressor of cytokine signaling 3 (SOCS3) increased for EDL and soleus muscles in OTR compared with C and TR. CONCLUSION: In summary, the current used OT protocol based on eccentric exercise sessions impaired the insulin signaling pathway with concomitant increases of IKK, SAPK/JNK, and SOCS3 protein levels.

Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats.

Hypothalamic inflammation is associated with insulin and leptin resistance, hyperphagia, and obesity. In this scenario, hypothalamic protein tyrosine phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation that is responsible for the central insulin and leptin resistance. Here, we demonstrated that acute exercise reduced inflammation and PTP1B protein level/activity in the hypothalamus of obese rodents. Exercise disrupted the interaction between PTP1B with proteins involved in the early steps of insulin (IRß and IRS-1) and leptin (JAK2) signaling, increased the tyrosine phosphorylation of these molecules, and restored the anorexigenic effects of insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and the reduction of PTP1B activity mediated by exercise occurred in an interleukin-6 (IL-6)-dependent manner because exercise failed to reduce inflammation and PTP1B protein level after the disruption of hypothalamic-specific IL-6 action in obese rats. Conversely, intracerebroventricular administration of recombinant IL-6 reproduced the effects of exercise, improving hypothalamic insulin and leptin action by reducing the inflammatory signaling and PTP1B activity in obese rats at rest. Taken together, our study reports that physical exercise restores insulin and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein level through the central anti-inflammatory response.

Resveratrol and fish oil reduce catecholamine-induced mortality in obese rats: role of oxidative stress in the myocardium and aorta.

The exact mechanisms of the relationship between obesity and cardiovascular events are not yet fully understood; however, oxidative stress may be involved. Thus, the aim of the present study was to evaluate the effects of resveratrol and fish oil on catecholamine-induced mortality in obese rats. To begin with, rats were divided into five groups: (1) lean, (2) obese, (3) obese supplemented with resveratrol, (4) obese supplemented with fish oil and (5) obese supplemented with resveratrol and fish oil (n 18 rats per group), for 2 months. After supplementation, the groups were subdivided as with (n 10) and without (n 8) cardiovascular catecholaminergic stress after isoproterenol (60 mg/kg) injection. At 24 h later, the survival rate was analysed. The obese group showed lower survival rates (10 %) when compared with the lean group (70 %). On the other hand, resveratrol (50 %) and fish oil (40 %) increased the survival rate of obese rats (χ(2) test, P= 0·019). Biochemical analyses of the myocardium and aorta revealed that obese rats had higher levels of superoxide and oxidative damage to lipids and protein. This was associated with reduced superoxide dismutase and glutathione peroxidase activity in both the myocardium and aorta. The supplementation increased antioxidant enzyme activities and reduced oxidative damage. We also evaluated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 antioxidant pathway. Nrf2 protein levels that were reduced in obese rats were increased by the antioxidant treatment. Taken together, these results showed that resveratrol and fish oil reduce catecholamine-induced mortality in obese rats, partly through the reduction of oxidative stress.

Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise.

Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline + 48 h); and eccentric exercise plus Cr 48 h (Cr + 48 h). Cr supplementation was administered as a solution of 300 mg · kg body weight(-1) · day(-1) in 1 mL water, for two weeks, before the eccentric exercise. The animals were submitted to one downhill run session at 1.0 km · h(-1) until exhaustion. Twenty-four and forty-eight hours after the exercise, the animals were killed, and the quadriceps were removed. Creatine kinase levels, superoxide production, thiobarbituric acid reactive substances (TBARS) level, carbonyl content, total thiol content, superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL-1ß), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were analysed. Cr supplementation neither decreases Cr kinase, superoxide production, lipoperoxidation, carbonylation, total thiol, IL-1ß, NF-kb, or TNF nor alters the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides in relation to the saline group, respectively (P < 0.05). There are positive correlations between Cr kinase and TBARS and TNF-α 48 hours after eccentric exercise. The present study suggests that Cr supplementation does not decrease oxidative stress and inflammation after eccentric contraction.

Green tea extract supplementation induces the lipolytic pathway, attenuates obesity, and reduces low-grade inflammation in mice fed a high-fat diet.

The aim of this study was to evaluate the effects of green tea Camellia sinensis extract on proinflammatory molecules and lipolytic protein levels in adipose tissue of diet-induced obese mice. Animals were randomized into four groups: CW (chow diet and water); CG (chow diet and water + green tea extract); HW (high-fat diet and water); HG (high-fat diet and water + green tea extract). The mice were fed ad libitum with chow or high-fat diet and concomitantly supplemented (oral gavage) with 400 mg/kg body weight/day of green tea extract (CG and HG, resp.). The treatments were performed for eight weeks. UPLC showed that in 10 mg/mL green tea extract, there were 15 µg/mg epigallocatechin, 95 µg/mg epigallocatechin gallate, 20.8 µg/mg epicatechin gallate, and 4.9 µg/mg gallocatechin gallate. Green tea administered concomitantly with a high-fat diet increased HSL, ABHD5, and perilipin in mesenteric adipose tissue, and this was associated with reduced body weight and adipose tissue gain. Further, we observed that green tea supplementation reduced inflammatory cytokine TNFα levels, as well as TLR4, MYD88, and TRAF6 proinflammatory signalling. Our results show that green tea increases the lipolytic pathway and reduces adipose tissue, and this may explain the attenuation of low-grade inflammation in obese mice.

Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice.

Accumulating evidence has demonstrated that S-nitrosation of proteins plays a critical role in several human diseases. Here, we explored the role of inducible nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the early steps of the insulin-signaling pathway and insulin resistance in the skeletal muscle of aged mice. Aging increased iNOS expression and S-nitrosation of major proteins involved in insulin signaling, thereby reducing insulin sensitivity in skeletal muscle. Conversely, aged iNOS-null mice were protected from S-nitrosation-induced insulin resistance. Moreover, pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S-nitrosation and increased insulin sensitivity in the muscle of aged animals. These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S-nitrosation of the insulin-signaling pathway.