Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.

High-fat diet (HFD) feeding in rodents has become an essential tool to critically analyze and study the pathological effects of obesity, including mitochondrial dysfunction and insulin resistance. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates cellular energy metabolism to influence insulin sensitivity, beyond its active role in stimulating mitochondrial biogenesis to facilitate skeletal muscle adaptations in response to HFD feeding. Here, some of the major electronic databases like PubMed, Embase, and Web of Science were accessed to update and critically discuss information on the potential role of PGC-1α during metabolic adaptations within the skeletal muscle in response to HFD feeding in rodents. In fact, available evidence suggests that partial exposure to HFD feeding (potentially during the early stages of disease development) is associated with impaired metabolic adaptations within the skeletal muscle, including mitochondrial dysfunction and reduced insulin sensitivity. In terms of implicated molecular mechanisms, these negative effects are partially associated with reduced activity of PGC-1α, together with the phosphorylation of protein kinase B and altered expression of genes involving nuclear respiratory factor 1 and mitochondrial transcription factor A within the skeletal muscle. Notably, metabolic abnormalities observed with chronic exposure to HFD (likely during the late stages of disease development) may potentially occur independently of PGC-1α regulation within the muscle of rodents. Summarized evidence suggests the causal relationship between PGC-1α regulation and effective modulations of mitochondrial biogenesis and metabolic flexibility during the different stages of disease development. It further indicates that prominent interventions like caloric restriction and physical exercise may affect PGC-1α regulation during effective modulation of metabolic processes.

High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

Anti-Obesity Effects of Metformin: A Scoping Review Evaluating the Feasibility of Brown Adipose Tissue as a Therapeutic Target.

Brown adipose tissue (BAT) is increasingly recognized as the major therapeutic target to promote energy expenditure and ameliorate diverse metabolic complications. There is a general interest in understanding the pleiotropic effects of metformin against metabolic complications. Major electronic databases and search engines such as PubMed/MEDLINE, Google Scholar, and the Cochrane library were used to retrieve and critically discuss evidence reporting on the impact of metformin on regulating BAT thermogenic activity to ameliorate complications linked with obesity. The summarized evidence suggests that metformin can reduce body weight, enhance insulin sensitivity, and improve glucose metabolism by promoting BAT thermogenic activity in preclinical models of obesity. Notably, this anti-diabetic agent can affect the expression of major thermogenic transcriptional factors such as uncoupling protein 1 (UCP1), nuclear respiratory factor 1 (NRF1), and peroxisome-proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) to improve BAT mitochondrial function and promote energy expenditure. Interestingly, vital molecular markers involved in glucose metabolism and energy regulation such as AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21) are similarly upregulated by metformin treatment in preclinical models of obesity. The current review also discusses the clinical relevance of BAT and thermogenesis as therapeutic targets. This review explored critical components including effective dosage and appropriate intervention period, consistent with the beneficial effects of metformin against obesity-associated complications.

Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature.

Chronic inflammation remains an essential complication in the pathogenesis and aggravation of metabolic diseases. There is a growing interest in the use of medicinal plants or food-derived bioactive compounds for their antioxidant and anti-inflammatory properties to improve metabolic function. For example, rutin, a flavonol derivative of quercetin that is found in several medicinal plants and food sources has displayed therapeutic benefits against diverse metabolic diseases. Here, we searched the major electronic databases and search engines such as PubMed/MEDLINE, Scopus and Google Scholar to systematically extract and critically discuss evidence reporting on the impact of rutin against metabolic diseases by affecting inflammation. In fact, available preclinical evidence suggests that rutin, through its strong antioxidant properties, can effectively ameliorate inflammation by reducing the levels of pro-inflammatory markers such as tumor necrosis factor-α, interleukin (IL)-6, cyclooxygenase-2, IL-1ß, as well as blocking nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) activation to improve metabolic function. Notably, although clinical data on the impact of rutin on inflammation is limited, food-derived sources rich in this flavonol such as Fagopyrum tataricum, Coffea arabica and Aspalathus linearis (rooibos) have shown promise in improving metabolic function, in part by reducing markers of oxidative stress and inflammation. However, additional studies are still required to confirm the therapeutic properties of rutin in a clinical setting, including the enhancement of it low bioavailability profile.

Epigallocatechin gallate as a nutraceutical to potentially target the metabolic syndrome: novel insights into therapeutic effects beyond its antioxidant and anti-inflammatory properties.

Epigallocatechin gallate (EGCG) is one of the most abundant and powerful flavonoids contained in green tea. Because of the global increase in green tea consumption, there has been a general interest in understanding its health benefits, including its bioactive compounds like EGCG. Indeed, preclinical evidence already indicates that EGCG demonstrated a strong antioxidant and anti-inflammatory properties that could be essential in protecting against metabolic syndrome. The current review explores clinical evidence reporting on the beneficial effects of EGCG supplementation in obese subjects or patients with diverse metabolic complications that include type 2 diabetes and cardiovascular disease. The discussion incorporates the impact of different formulations of EGCG, as well as the effective doses and treatment duration. Importantly, besides highlighting the potential use of EGCG as a nutraceutical, the current review also discusses crucial evidence related to its pharmaceutical development as an agent to hinder metabolic diseases, including its bioavailability and metabolism profile, as well as its well-known biological properties.

Adipokines as a therapeutic target by metformin to improve metabolic function: A systematic review of randomized controlled trials.

Metformin is a widely used glucose-lowering drug, although its impact on adipose tissue function remains elusive. Adipose tissue-derived molecules regulate diverse physiological mechanisms, including energy metabolism, insulin sensitization, and inflammatory response. Alternatively, it has remained relevant to understand the therapeutic regulation of adipokines in efforts to alleviate inflammation in conditions associated with the metabolic syndrome. The current qualitative analysis of available literature focused on randomized clinical trials (RCTs) assessing the association between administration of metformin and adipokine regulation in individuals with metabolic syndrome. The major electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible RCTs. Overall, 13 RCTs met the inclusion criteria, with a total of 4605 participants. Patients with metabolic syndrome were characterized by a state of obesity, impaired glucose tolerance, insulin resistance, and type 2 diabetes. Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-α in patients with metabolic syndrome. Importantly, these therapeutic effects are associated with the upregulation of adiponectin and suppression of leptin and resistin.

Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells.

Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes.

The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models.

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

Isoorientin: A dietary flavone with the potential to ameliorate diverse metabolic complications.

Isoorientin is a natural C-glucosyl flavone that is generating a lot of interest due to its multiple pharmacological activities. Increasing experimental data have shown that the robust antioxidant and anti-inflammatory properties of isoorientin remain important in ameliorating a number of metabolic complications. In fact, plants rich in isoorientin have demonstrated strong ameliorative properties against complications such as hyperglycemia, hyperlipidemia, and insulin resistance. However, while such evidence is accumulating, it has not been reviewed to better inform on the therapeutic potential of this flavone in improving human health. This review examines and extrapolates available literature on the potential beneficial or detrimental effects associated with the use of isoorientin in mitigating metabolic diseases, with a specific focus on diabetes, obesity, and insulin resistance, including associated complications. The discussion includes effective doses in various experimental settings and proposed molecular mechanisms by which isoorientin may exert its therapeutic effects. In addition, the protective effects of extracts of a number of isoorientin-rich plants against metabolic complications will be highlighted.

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes.

The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1-100 µM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 µM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.

Brown adipose tissue-derived metabolites and their role in regulating metabolism.

The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.

Corrigendum: A review on the antidiabetic properties of Moringa oleifera extracts: Focusing on oxidative stress and inflammation as main therapeutic targets.

[This corrects the article DOI: 10.3389/fphar.2022.940572.].

Disease progression promotes changes in adipose tissue signatures in type 2 diabetic (db/db) mice: The potential pathophysiological role of batokines.

Unlike the white adipose tissue (WAT) which mainly stores excess energy as fat, brown adipose tissue (BAT) has become physiologically important and therapeutically relevant for its prominent role in regulating energy metabolism. The current study makes use of an established animal model of type 2 diabetes (T2D) db/db mice to determine the effect of the disease progression on adipose tissue morphology and gene regulatory signatures. Results showed that WAT and BAT from db/db mice display a hypertrophied phenotype that is consistent with increased expression of the pro-inflammatory cytokine, tumor necrosis factor-alpha (Tnf-α). Moreover, BAT from both db/db and non-diabetic db/+ control mice displayed an age-related impairment in glucose homeostasis, inflammatory profile, and thermogenic regulation, as demonstrated by reduced expression of genes like glucose transporter (Glut-4), adiponectin (AdipoQ), and uncoupling protein 1 (Ucp-1). Importantly, gene expression of the batokines regulating sympathetic neurite outgrowth and vascularization, including bone morphogenic protein 8b (Bmp8b), fibroblast growth factor 21 (Fgf-21), neuregulin 4 (Nrg-4) were altered in BAT from db/db mice. Likewise, gene expression of meteorin-like (Metrnl), growth differentiation factor 15 (Gdt-15), and C-X-C motif chemokine-14 (Cxcl-14) regulating pro- and anti-inflammation were altered. This data provides some new insights into the pathophysiological mechanisms involved in BAT hypertrophy (or whitening) and the disturbances of batokines during the development and progression of T2D. However, these are only preliminary results as additional experiments are necessary to confirm these findings in other experimental models of T2D.

Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials.

Cardiovascular diseases (CVDs) continue to be the leading cause of death in people with diabetes mellitus. Severely suppressed intracellular antioxidant defenses, including low plasma glutathione (GSH) levels, are consistently linked with the pathological features of diabetes such as oxidative stress and inflammation. In fact, it has already been established that low plasma GSH levels are associated with increased risk of CVD in people with diabetes. Dietary supplements are widely used and may offer therapeutic benefits for people with diabetes at an increased risk of developing CVDs. However, such information remains to be thoroughly scrutinized. Hence, the current systematic review explored prominent search engines, including PubMed and Google Scholar, for updated literature from randomized clinical trials reporting on the effects of dietary supplements on plasma GSH levels in people with diabetes. Available evidence indicates that dietary supplements, such as coenzyme Q10, selenium, curcumin, omega-3 fatty acids, and vitamin E or D, may potentially improve cardiometabolic health in patients with diabetes. Such beneficial effects are related to enhancing plasma GSH levels and reducing cholesterol, including biomarkers of oxidative stress and inflammation. However, available evidence is very limited and additional clinical studies are still required to validate these findings, including resolving issues related to the bioavailability of these bioactive compounds.

Impact of dyslipidemia in the development of cardiovascular complications: Delineating the potential therapeutic role of coenzyme Q10.

Dyslipidemia is one of the major risk factors for the development of cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). This metabolic anomality is implicated in the generation of oxidative stress, an inevitable process involved in destructive mechanisms leading to myocardial damage. Fortunately, commonly used drugs like statins can counteract the detrimental effects of dyslipidemia by lowering cholesterol to reduce CVD-risk in patients with T2D. Statins mainly function by blocking the production of cholesterol by targeting the mevalonate pathway. However, by blocking cholesterol synthesis, statins coincidently inhibit the synthesis of other essential isoprenoid intermediates of the mevalonate pathway like farnesyl pyrophosphate and coenzyme Q10 (CoQ10). The latter is by far the most important co-factor and co-enzyme required for efficient mitochondrial oxidative capacity, in addition to its robust antioxidant properties. In fact, supplementation with CoQ10 has been found to be beneficial in ameliorating oxidative stress and improving blood flow in subjects with mild dyslipidemia.. Beyond discussing the destructive effects of oxidative stress in dyslipidemia-induced CVD-related complications, the current review brings a unique perspective in exploring the mevalonate pathway to block cholesterol synthesis while enhancing or maintaining CoQ10 levels in conditions of dyslipidemia. Furthermore, this review disscusses the therapeutic potential of bioactive compounds in targeting the downstream of the mevalonate pathway, more importantly, their ability to block cholesterol while maintaining CoQ10 biosynthesis to protect against the destructive complications of dyslipidemia.

Pancreatic ß-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress.

Insulin resistance and pancreatic ß-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define ß-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1ß are consistently associated with ß-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic ß-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of ß-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during ß-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve ß-cell function.

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin.

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as a potential avenue to combat obesity. Although BAT is the opposite of white adipose tissue (WAT) which is responsible for energy storage, BAT shares thermogenic capacity with beige adipose tissue that emerges from WAT depots. This is unsurprising as both BAT and beige adipose tissue display a huge difference from WAT in terms of their secretory profile and physiological role. In obesity, the content of BAT and beige adipose tissue declines as these tissues acquire the WAT characteristics via the process called "whitening". This process has been rarely explored for its implication in obesity, whether it contributes to or exacerbates obesity. Emerging research has demonstrated that BAT/beige adipose tissue whitening is a sophisticated metabolic complication of obesity that is linked to multiple factors. The current review provides clarification on the influence of various factors such as diet, age, genetics, thermoneutrality, and chemical exposure on BAT/beige adipose tissue whitening. Moreover, the defects and mechanisms that underpin the whitening are described. Notably, the BAT/beige adipose tissue whitening can be marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation.

Sarcopenia in a type 2 diabetic state: Reviewing literature on the pathological consequences of oxidative stress and inflammation beyond the neutralizing effect of intracellular antioxidants.

Sarcopenia remains one of the major pathological features of type 2 diabetes (T2D), especially in older individuals. This condition describes gradual loss of muscle mass, strength, and function that reduces the overall vitality and fitness, leading to increased hospitalizations and even fatalities to those affected. Preclinical evidence indicates that dysregulated mitochondrial dynamics, together with impaired activity of the NADPH oxidase system, are the major sources of oxidative stress that drive skeletal muscle damage in T2D. While patients with T2D also display relatively higher levels of circulating inflammatory markers in the serum, including high sensitivity-C-reactive protein, interleukin-6, and tumor necrosis factor-α that are independently linked with the deterioration of muscle function and sarcopenia in T2D. In fact, beyond reporting on the pathological consequences of both oxidative stress and inflammation, the current review highlights the importance of strengthening intracellular antioxidant systems to preserve muscle mass, strength, and function in individuals with T2D.

A Review on the Antidiabetic Properties of Moringa oleifera Extracts: Focusing on Oxidative Stress and Inflammation as Main Therapeutic Targets.

Moringa oleifera is one of the popular plants that have shown significant health benefits. Certainly, preclinical evidence (predominantly from animal models) summarized in the current review supports the beneficial effects of Moringa oleifera leaf extracts in combating the prominent characteristic features of diabetes mellitus. This includes effective control of blood glucose or insulin levels, enhancement of insulin tissue sensitivity, improvement of blood lipid profiles, and protecting against organ damage under sustained conditions of hyperglycemia. Interestingly, as major complications implicated in the progression of diabetes, including organ damage, Moringa oleifera leaf and seed extracts could efficiently block the detrimental effects of oxidative stress and inflammation in these preclinical models. Notably, these extracts (especially leaf extracts) showed enhanced effects in strengthening intracellular antioxidant defences like catalase, superoxide dismutase, and glutathione to lower lipid peroxidation products and reduce prominent pro-inflammatory markers such as tumor necrosis factor-α, interleukin (1L)-ß, IL-6, monocyte chemoattractant protein-1 and nitric oxide synthase. From animal models of diabetes, the common and effective dose of leaf extracts of Moringa oleifera was 100-300 mg/kg, within the treatment duration of 2-8 weeks. Whereas supplementation with approximately 20 g leaf powder of Moringa oleifera for at least 2 weeks could improve postprandial blood glucose in subjects with prediabetes or diabetes. Although limited clinical studies have been conducted on the antidiabetic properties of Moringa oleifera, current findings provide an important platform for future research directed at developing this plant as a functional food to manage diabetic complications.

Impact of physical exercise and caloric restriction in patients with type 2 diabetes: Skeletal muscle insulin resistance and mitochondrial dysfunction as ideal therapeutic targets.

Skeletal muscle insulin resistance and mitochondrial dysfunction are some of the major pathological defects implicated in the development of type 2 diabetes (T2D). Therefore, it has become necessary to understand how common interventions such as physical exercise and caloric restriction affect metabolic function, including physiological processes that implicate skeletal muscle dysfunction within a state of T2D. This review critically discusses evidence on the impact of physical exercise and caloric restriction on markers of insulin resistance and mitochondrial dysfunction within the skeletal muscle of patients with T2D or related metabolic complications. Importantly, relevant information from clinical studies was acquired through a systematic approach targeting major electronic databases and search engines such as PubMed, Google Scholar, and Cochrane library. The reported evidence suggests that interventions like physical exercise and caloric restriction, within a duration of approximately 2 to 4 months, can improve insulin sensitivity, in part by targeting the phosphoinositide 3-kinases/protein kinase B pathway in patients with T2D. Furthermore, both physical exercise and caloric restriction can effectively modulate markers related to improved mitochondrial function and dynamics. This was consistent with an improved modulation of mitochondrial oxidative capacity and reduced production of reactive oxygen species in patients with T2D or related metabolic complications. However, such conclusions are based on limited evidence, additional clinical trials are required to better understand these interventions on pathological mechanisms of T2D and related abnormalities.