דו״ח מאומת

Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.…

PMID: 25620073

Moringa oleifera Lam. contains many active ingredients with nutritional and medicinal values. It is commonly used in folk medicine as an antidiabetic agent. The present study was designed to investigate how an aqueous extract from the leaves of M. oleifera reveals hypoglycemia in diabetic rats. M. oleifera leaf extract counteracted the alloxan-induced diabetic effects in rats as it normalized the elevated serum levels of glucose, triglycerides, cholesterol, and malondialdehyde, and normalized mRNA expression of the gluconeogenic enzyme pyruvate carboxylase in hepatic tissues. It also increased live body weight gain and normalized the reduced mRNA expression of fatty acid synthase in the liver of diabetic rats. Moreover, it restored the normal histological structure of the liver and pancreas damaged by alloxan in diabetic rats. This study revealed that the aqueous extract of M. oleifera leaves possesses potent hypoglycemic effects through the normalization of elevated hepatic pyruvate carboxylase enzyme and regeneration of damaged hepatocytes and pancreatic β cells via its antioxidant properties.…

PMID: 25289966

Ketogenic diets, which are high in fat, hold therapeutic promises in obesity and type 2 diabetes and are to be carefully studied in their early stages on healthy mouse models. This study evaluated the physiological, biochemical, histological, and genetic impacts of a Moringa oleifera-supplemented ketogenic meal replacement (KMR) compared with a commercial non-ketogenic meal replacement (CMR) and standard chow in female C57BL/6J mice (n = 8/group) over 20 weeks. Despite similar caloric intake, KMR-fed mice exhibited ~ 30% lower weight gain than both control and CMR groups, highlighting the role of macronutrient composition over energy content. Insulin sensitivity was preserved across groups, with KMR maintaining fasting glucose, insulin, and HOMA-IR < 0.4. KMR promoted favorable lipid remodeling, including elevated HDL cholesterol (128 ± 6 mg/dL), reduced LDL cholesterol (25 ± 2 mg/dL), and the lowest non-HDL cholesterol, yielding the most favorable HDL: LDL ratio. Liver enzyme analysis revealed hepatoprotective effects in KMR, contrasting with elevated ALT and AST in CMR. Renal biomarkers and the histological observations indicated mild disorder in kidney functions across CMR and KMR groups. At the molecular level, KMR upregulated ketogenesis genes (Hmgcs2, Bdh1), mitochondrial regulators (Sirt3, Fgf21), and the anti-inflammatory cytokine IL10. Conversely, CMR downregulated Bdh1, Fgf21, and IL10 while exerting negligible or nonsignificant effects on Hmgcs2 and Sirt3. Collectively, KMR attenuated weight gain and improved lipid metabolism maintaining insulin and blood glucose levels. This supports its effective dietary management for type 2 diabetes. However, given the observed histological changes, further long-term studies are recommended to confirm the safety of the ketogenic diet on organ tissues.…

PMID: 41605998

Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.…

PMID: 25620073

Obesity is considered a chronic disease that co-occurs with other disorders, including type 2 diabetes; therefore, the prevention and treatment of obesity are of utmost importance. The present review analysed the effects of bioactive compounds found in culinary herbs on the regulation of inflammatory processes through the modulation of inflammation and microbiota-dependent metabolic pathways. A total of 137 publications from 2010 to 2025 were reviewed. Few studies address the impact of culinary herbs on the gut microbiota in relation to obesity; however, analysing data on the effects of active compounds present in various herbs allows an assessment of their potential role in obesity prevention. This is a significant issue, as obesity is widespread, and the introduction of readily usable everyday food products may represent an important element of preventive strategies. Plant secondary metabolites, such as polyphenols, saponins, alkaloids, and flavonoids, exert strong antioxidant and anti-inflammatory activity, thus contributing to their beneficial effects on human health. Effective weight loss depends on the consistent maintenance of a healthy lifestyle, a requirement that can often be highly challenging. The daily use of herbs in meal preparation may reduce the risk of developing obesity or mitigate its severity. Herbs enhance the flavour of dishes and, additionally, help to reduce salt intake, thereby lowering the risk of cardiovascular disease, which is also an integral component of a healthy lifestyle.…

PMID: 41901168

<i>Moringa oleifera,</i> widely recognized as the horseradish tree or drumstick tree, is classified within the <i>Moringaceae</i> family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of <i>Moringa oleifera</i> and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of <i>Moringa oleifera</i>, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant's effect on the immune response via different pathways. Several studies indicate that <i>Moringa oleifera</i> mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that <i>Moringa oleifera</i> can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8⁺ and CD4⁺ T lymphocytes. Together, <i>Moringa oleifera</i> could be considered for the treatment of conditions related to immune dysregulation, such as cancer.…

PMID: 41516140

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic and environmental features in their pathogenesis, obesity amplifies the impact of genetic susceptibility and environmental factors on DM. The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional β-cells and gradual elevation of blood glucose. Given these intricate connections, most available treatments of obesity and type 2 DM (T2DM) have a mutual effect on each other. For example, anti-obesity drugs can be anti-diabetic to some extent, and some anti-diabetic medicines, in contrast, have been shown to increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both obesity and T2DM. Besides guaranteeing the availability and accessibility of all the available diagnostic and therapeutic tools, more clinical and experimental investigations on the pathogenesis of these two diseases are warranted to improve the efficacy and safety of the available and newly developed treatments.…

PMID: 37152942

Genetic, environmental, and metabolic risk factors are interrelated and contribute to the development of type 2 diabetes mellitus. A strong family history of diabetes mellitus, age, obesity, and physical inactivity identify those individuals at highest risk. Minority populations are also at higher risk, not only because of family history and genetics, but also because of adaptation to American environmental influences of poor dietary and exercise habits. Women with a history of gestational diabetes as well as their children are at greater risk for progressing to type 2 diabetes mellitus. Insulin resistance increases a person's risk for developing impaired glucose tolerance and type 2 diabetes. Individuals who have insulin resistance share many of the same risk factors as those with type 2 diabetes. These include hyperinsulinemia, atherogenic dyslipidemia, glucose intolerance, hypertension, prothrombic state, hyperuricemia, and polycystic ovary syndrome. Current interventions for the prevention and retardation of type 2 diabetes mellitus are those targeted towards modifying environmental risk factors such as reducing obesity and promoting physical activity. Awareness of risk factors for developing type 2 diabetes will promote screening, early detection, and treatment in high-risk populations with the goal of decreasing both microvascular and macrovascular complications.…

PMID: 11800065

Epigenetic mechanisms control gene activity and the development of an organism. The epigenome includes DNA methylation, histone modifications, and RNA-mediated processes, and disruption of this balance may cause several pathologies and contribute to obesity and type 2 diabetes (T2D). This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism-i.e., adipose tissue, skeletal muscle, pancreatic islets, liver, and blood-in relation to obesity and T2D. Although this research field is still young, these comprehensive data support not only a role for epigenetics in disease development, but also epigenetic alterations as a response to disease. Genetic predisposition, as well as aging, contribute to epigenetic variability, and several environmental factors, including exercise and diet, further interact with the human epigenome. The reversible nature of epigenetic modifications holds promise for future therapeutic strategies in obesity and T2D.…

PMID: 30982733

The epidemic rise in obesity has fuelled the current debate over its classification as a disease. Contrary to just being a medical condition or risk factor for other diseases, obesity is a complex disease of multifaceted aetiology, with its own disabling capacities, pathophysiologies and comorbidities. It meets the medical definition of disease in that it is a physiological dysfunction of the human organism with environmental, genetic and endocrinological aetiologies. It is a response to environmental stimuli, genetic predisposition and abnormalities, and has a characteristic set of signs and symptoms with consistent anatomical alterations. Excess adipose tissue increases the work of the heart and leads to anatomical changes in this organ. It alters pulmonary, endocrine and immunological functions, all with adverse effects on health. Some of the complications of obesity include cardiovascular disease, non-insulin-dependent diabetes mellitus, obstructive pulmonary disease, arthritis and cancer. Given the excess mortality, substantial morbidity and the economic toll of obesity, this is a disease that warrants serious attention by the medical community. Obesity's status and acceptance as a disease is pivotal in determining its treatment, reimbursement for treatment and the development of widespread interventions.…

PMID: 15245383

Low-grade chronic inflammation (LGCI) is increasingly recognized as a silent yet significant contributor to the global burden of non-communicable diseases. Traditionally associated with aging, emerging evidence indicates that LGCI is now prevalent among young adults due to modern lifestyle patterns. Factors such as sedentary behavior, ultra-processed food consumption, obesity, chronic psychological stress, sleep deprivation, environmental pollutants, and altered gut microbiota contribute to a persistent state of systemic inflammation. Unlike acute inflammation, which is protective and self-limiting, LGCI is characterized by subtle but continuous elevation of inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). In young populations, this chronic inflammatory milieu often remains clinically unnoticed but may predispose individuals to a range of metabolic, cardiovascular, neuropsychiatric, and reproductive disorders later in life. Recent epidemiological studies suggest that early exposure to inflammatory triggers accelerates the development of insulin resistance, endothelial dysfunction, and immune dysregulation. Additionally, lifestyle transitions associated with urbanization and digital dependence have intensified inflammatory risk factors among young adults worldwide. Recognizing LGCI as an early biological warning signal offers opportunities for preventive interventions. Dietary modulation, physical activity, adequate sleep, stress management, and gut microbiome optimization have shown promise in reducing inflammatory burden. Early screening of inflammatory biomarkers in high-risk young individuals may further aid in identifying subclinical disease risk. Increased awareness among clinicians and public health professionals is essential to address this emerging concern. This perspective highlights the importance of acknowledging low-grade chronic inflammation in young adults as an underrecognized epidemic and emphasizes the need for early preventive strategies to mitigate long-term health consequences.…

PMID: 41818927

Systemic inflammation induced by adipose tissue is common in obese individuals and is often overlooked due to its subclinical nature. The constant secretion of proinflammatory factors shifts the balance toward inflammation, affecting the body's homeostasis and facilitating the development of various chronic diseases. In the liver, proinflammatory markers, free fatty acids (FFAs), and the hormone leptin, all of which originate from adipose tissue, trigger an inflammatory response that favors fibrogenesis. Conversely, serum levels of proinflammatory factors can be used to assess both the risk of liver fibrosis and the effectiveness of treatment. Their application is straightforward due to their non-invasive nature, but it is important to confirm their reliability in future investigations. Moreover, dietary approaches to therapy, along with physical activity, deserve more attention as their effectiveness has frequently been demonstrated and they are recommended by official guidelines. The focus on reducing body weight through fat loss is especially crucial. To enhance the quality and value of dietary strategies in therapy, it is also necessary to refine and expand their potential.…

PMID: 41660515

The global increase in early-onset cancers among adolescents and young adults has happened at the same time as the rise in the consumption of ultra-processed foods (UPFs). Far beyond their poor nutritional quality, UPFs are increasingly seen as Trojan horses, complex biological agents that interfere with many functions of the human organism. In this review, we utilise the Trojan horse model to explain the quiet and building health risks from UPFs as foods that seem harmless, convenient, and affordable while secretly delivering endocrine-disrupting chemicals (EDCs), causing chronic low-grade inflammation, altering the microbiome, and producing epigenetic alterations. We bring together new proof showing that UPFs mess up hormonal signals, harm the body's ability to fight off harmful germs, lead to an imbalance of microbes, and cause detrimental changes linked to cancer. Important components, such as bisphenols and phthalates, can migrate from containers into food, while additional ingredients and effects from cooking disrupt the normal balance of cells. These exposures are especially harmful during vulnerable developmental periods and may lay the groundwork for disease many years later. The Trojan horse model illustrates the hidden nature of UPF-related damage, not through a sudden toxin but via chronic dysregulation of metabolic, hormonal, and genetic control. This model changes focus from usual diet worries to a bigger-picture view of UPFs as causes of life-disrupting damage. Ultimately, this review aims to identify gaps in current knowledge and epidemiological approaches and highlight the need for multi-omics, long-term studies and personalised nutrition plans to assess and reduce the cancer risk associated with UPFs. Recognising UPFs as a silent disruptor is crucial in shaping public health policies and cancer prevention programs targeting younger people.…

PMID: 40647494

This article examines the human body's adaptive responses to obesity from biological, behavioral, and evolutionary perspectives. It explores how ancient survival mechanisms, such as fat storage during scarcity, have persisted but become maladaptive in modern contexts of food abundance and sedentary lifestyles. Using the Thrifty Gene Hypothesis and General Adaptation Syndrome (GAS), the study investigates how chronic stress and genetic predispositions contribute to obesity. Chronic stress, as described in GAS, is linked to obesity through mechanisms like prolonged cortisol elevation, which promotes fat storage, particularly in the abdominal region, and disrupts hunger and satiety regulation. The article also explores the possibility that contemporary chronic stress may cause the body to buffer stressful conditions through fat accumulation. While the Thrifty Gene Hypothesis suggests that genetic traits evolved to optimize energy storage during scarcity, contributing to obesity in modern environments, it remains controversial. Critics argue that it oversimplifies obesity's causes, such as lifestyle and environmental factors. Although genetic variations influencing obesity susceptibility continue to evolve, the physiological mechanisms of fat storage and stress adaptation have remained largely unchanged since ancient times.…

PMID: 40287541

Human survival has relied upon the ability to withstand starvation through energy storage, the capacity to fight off infection by a proinflammatory immune response, and the ability to cope with physical stressors by an adaptive stress response. Energy storage, mainly as glycogen in liver and triglycerides in adipose tissue, is regulated by the anabolic actions of insulin. On the other hand, mobilization of stored energy during infection, trauma or stress is served by the temporary inhibition of insulin action (insulin resistance) in target tissues by proinflammatory cytokines and stress hormones. In the current environment, high energy intake, low physical activity, and chronic stress favor the storage of surplus fat in adipose tissue depots that far exceeds their storage capacity and liporegulation. Lipid overload in central fat depots initiates an inflammatory response and adipocyte dysfunction with resultant low-grade systemic inflammation and lipid overflow to peripheral tissues. In turn, proinflammatory cytokines and non-oxidized lipid metabolites, accumulated in liver and muscle cells, activate the mechanism of insulin resistance as would occur in the case of infection or stress. The same factors together with the ensuing insulin resistance further contribute to pancreatic β-cell dysfunction and ultimately to type 2 diabetes and cardiovascular disease. The present review supports the hypothesis that insulin resistance evolved as a physiological adaptive mechanism in human survival and that the same mechanism is inappropriately activated on a chronic basis in the current environment, leading to the manifestations of the metabolic syndrome.…

PMID: 23260798

Sepsis remains a critical global health challenge characterized by high mortality and morbidity, primarily due to the limitations of current pathogen-centric therapies and a poor understanding of host-defense mechanisms. This review synthesizes the pivotal role of the adipose-immune-metabolic axis as a central regulator of disease tolerance-a host defense strategy that limits tissue damage without directly reducing pathogen load. We delineate how adipose tissue is reprogrammed from a passive energy reservoir into an active immunometabolic hub during sepsis. This functional shift is governed by three core hypotheses: "Metabolic Defense Priority," which describes the preferential mobilization of fat to spare skeletal muscle protein; "Bidirectional Immunometabolic Crosstalk," wherein immune cells such as macrophages and B cells precisely regulate lipolysis via specific cytokine signals (e.g., IL-1β and TGF-β); and "Stage-Specific Adaptation," which outlines the dynamic evolution of axis function from the acute to chronic phases of sepsis. We further dissect key molecular pathways, including the Insulin-INSR-Thermogenesis, TGFβ-PDE3b-cAMP, and STING-ER Stress-mtROS axes, that orchestrate this complex interplay. Finally, we discuss contemporary challenges in mechanistic understanding, model translatability, and clinical translation, while proposing future directions to leverage this axis for developing novel, tolerance-based therapeutic strategies to improve sepsis outcomes.…

PMID: 41853269