The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. In recent years, animal studies and clinical studies have shown that some lactic acid bacteria possess an anti-obesity effect. In our previous study, mixed lactobacilli (Lactobacillus plantarum KLDS1.0344 and Lactobacillus plantarum KLDS1.0386) exhibited anti-obesity effects in vivo by significantly reducing body weight gain, Lee's index and body fat rate; however, its underlying mechanisms of action remain unclear. Therefore, the present study aims to explore the possible mechanisms for the inhibitory effect of mixed lactobacilli on obesity. C57BL/6J mice were randomly divided into three groups including control group (Control), high fat diet group (HFD) and mixed lactobacilli group (MX), and fed daily for eight consecutive weeks. The results showed that mixed lactobacilli supplementation significantly improved blood lipid levels and liver function, and alleviated liver oxidative stress. Moreover, the mixed lactobacilli supplementation significantly inhibited lipid accumulation in the liver and regulated lipid metabolism in epididymal fat pads. Notably, the mixed lactobacilli treatment modulated the gut microbiota, resulting in a significant increase in acetic acid and butyric acid. Additionally, Spearman's correlation analysis found that several specific genera were significantly correlated with obesity-related indicators. These results indicated that the mixed lactobacilli supplementation could manipulate the gut microbiota and its metabolites (acetic acid and butyric acid), resulting in reduced liver lipid accumulation and improved lipid metabolism of adipose tissue, which inhibited obesity.

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Probiotic Mixture of Lactobacillus plantarum Strains Improves Lipid Metabolism and Gut Microbiota Structure in High Fat Diet-Fed Mice.

Scope Huangjinya is a light-sensitive tea mutant containing low levels of tea polyphenols. Currently, most studies focused on characteristics formation, free amino acid metabolism and phytochemical purification. The biological activity of Huangjinya black tea (HJBT) on metabolic syndrome regarding fecal metabolome modulation is unavailable and is studied herein. Methods and results High-fat diet (HFD)-fed mice are treated with HJBT for 9 weeks, various metabolic biomarkers and fecal metabolites are determined. HJBT reduces adipogenic and lipogenic gene expression, enhances lipolytic gene expression, decreases adipocyte expansion, and prevents the development of obesity. HJBT reduces lipogenic gene expression, increases fatty acid oxidation-related genes expression, which alleviates liver steatosis. HJBT enhances glucose/insulin tolerance, increases insulin/Akt signaling, attenuates hyperlipidemia and hyperglycemia, prevents the onset of insulin resistance. HJBT modulates bile acid metabolism, promotes secondary/primary bile acid ratio; increases short-chain fatty acids production, promotes saturated and polyunsaturated fatty acids content; reduces carnitines and phosphocholines, but increases myo-inositol content; decreases branched-chain and aromatic amino acids content; increases the metabolite content related to pentose phosphate pathway. Conclusion This study reported the association between fecal metabolome modulation and metabolism improvement due to HJBT administration, proposes HJBT as a dietary intervention for preventing obesity and metabolic disorders.

Huangjinya Black Tea Alleviates Obesity and Insulin Resistance via Modulating Fecal Metabolome in High-Fat Diet-Fed Mice.

Background. Along with the global prevalence of obesity, the associated health and economic impacts are rapidly multiplying. The challenge to primary care is to identify and treat obesity as a chronic disease. Patients should receive specific advice about diet, lifestyle, and physical activity rather than a vague or terse recommendation to simply eat less and exercise. Regular monitoring and follow-up visits are critical, as with any chronic disease. When nonpharmacologic methods do not lead to weight loss, select patients should be offered supplementary pharmacotherapy. Bariatric surgery is a safe and effective treatment for some patients with persistent severe obesity or obesity with complications despite nonpharmacologic efforts and medications.

Adult Obesity Management for Primary Care

Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. Methods: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.

The neurotherapeutic role of a selenium-functionalized quinoline in hypothalamic obese rats

The search for novel pancreatic lipase (PL) inhibitors has gained increasing attention in recent years. For the first time, a dual detection capillary electrophoresis (CE)-based homogeneous lipase assay was developed employing both the offline and online reaction modes. The hydrolysis of 4-nitrophenyl butyrate (4-NPB) catalyzed by PL into 4-nitrophenol and butyrate was monitored by spectrophotometric and conductimetric detection, respectively. The assays presented several advantages such as economy in consumption (few tens of nanoliters for online assays to few tens of microliters for offline assays), no modification of lipase, rapidity (<10 min) and versatility. Tris/MOPS (10 mM, pH 6.6) was used as the background electrolyte and the incubation buffer for enzymatic reactions. We confirmed that in the conditions of the study (small substrate 4-NPB, 37 °C, pH 6.6), the PL was active even in the absence of dipalmitoylphosphatidylcholine (DPPC) vesicles, generally used to mimic the lipid-water interface. This was confirmed by the maximum velocity (Vmax) and the Michaelis-Menten constant (Km) values that were the same order of magnitude in the absence and presence of DPPC. The developed method was used to screen crude aqueous plant extracts and purified compounds. We were able to identify the promising PL inhibition of hawthorn leaf herbal infusions at 1 mg mL-1 (37%) and PL activation by fresh and dry hawthorn flowers (∼24%). Additionally, two triterpenoids purified from extracts of oakwood were identified for the first time as potent PL inhibitors demonstrating 51 and 58% inhibition at 1 mg mL-1, respectively.

Screening for pancreatic lipase natural modulators by capillary electrophoresis hyphenated to spectrophotometric and conductometric dual detection.

Obesity is a severe worldwide epidemic. Obesity comorbidities, such as type 2 diabetes mellitus, hypertension, and atherosclerosis, are costly for patients and governments. The treatment of obesity involves several facets, including lifestyle changes, bariatric surgery, and pharmacotherapy. As changes in lifestyle require considerable patient commitment that is sometimes unachievable, and surgery is expensive and invasive, pharmacotherapy is the primary option for most patients. This review describes the pharmacotherapy currently available in the USA, Europe, and Brazil, focusing on its limitations. We then analyze the results from clinical trials of new drug candidates. Most drugs cause weight loss of < 4 kg compared with controls, and severe adverse effects have caused a number of drugs to be withdrawn from the market in several countries. Drugs under development have not shown more significant weight loss or reduced adverse effects. We conclude that a significant portion of obese patients have few treatment options because of the adverse effects and minimal weight loss associated with current pharmacotherapy. However, drugs currently under development appear unable to change this scenario in the near future. Thus, it is essential that new compounds are developed and new molecular targets studied so obesity can be efficiently treated in all patients in the future.

Pharmacotherapy of Obesity: Limits and Perspectives.

Typical of tropical and subtropical regions, malaria is caused by protozoa of the genus Plasmodium and is, still today, despite all efforts and advances in controlling the disease, a major issue of public health. Its clinical course can present either as the classic episodes of fever, sweating, chills and headache or as nonspecific symptoms of acute febrile syndromes and may evolve to severe forms. Survivors of cerebral malaria, the most severe and lethal complication of the disease, might develop neurological, cognitive and behavioral sequelae. This overview discusses the neurocognitive deficits and behavioral alterations resulting from human naturally acquired infections and murine experimental models of malaria. We highlighted recent reports of cognitive and behavioral sequelae of non-severe malaria, the most prevalent clinical form of the disease worldwide. These sequelae have gained more attention in recent years and therapies for them are required and demand advances in the understanding of neuropathogenesis. Recent studies using experimental murine models point to immunomodulation as a potential approach to prevent or revert neurocognitive sequelae of malaria.

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Malaria Related Neurocognitive Deficits and Behavioral Alterations

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.

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Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria

Malaria, an ancient infectious parasitic disease, is caused by protozoa of the genus Plasmodium, whose erythrocytic cycle is accompanied by fever, headache, sweating and chills and a systemic inflammation that can progress to severe forms of disease, including cerebral malaria. Approximately 25% of survivors of this syndrome develop sequelae that may include neurological, neurocognitive, behavioral alterations and poor school performance. Furthermore, some outcomes have also been recorded following episodes of non-severe malaria, which correspond to the most common clinical form of the disease worldwide. There is a body of evidence that neuroinflammation, due to systemic inflammation, plays an important role in the neuropathogenesis of malaria culminating in these cognitive dysfunctions. Preclinical studies suggest that vaccination with type 2 immune response elicitors, such as the tetanus-diphtheria (Td) vaccine, may exert a beneficial immunomodulatory effect by alleviating neuroinflammation. In this viewpoint article, vaccination is proposed as a therapy approach to revert or mitigate neurocognitive deficits associated with malaria. 

Immunomodulation through vaccination as a promising therapeutic strategy to mitigate malaria-related neurocognitive sequelae

The immune and nervous systems can be thought of as cognitive and plastic systems, since they are both involved in cognition/recognition processes and can be architecturally and functionally modified by experience, and such changes can influence each other's functioning. The immune system can affect nervous system function depending on the nature of the immune stimuli and the pro/anti-inflammatory responses they generate. Here we consider interactions between the immune and nervous systems in homeostasis and disease, including the beneficial and deleterious effects of immune stimuli on brain function and the impact of severe and non-severe malaria parasite infections on neurocognitive and behavioral parameters in human and experimental murine malaria. We also discuss the effect of immunization on the reversal of cognitive deficits associated with experimental non-severe malaria in a model susceptible to the development of the cerebral form of the illness. Finally, we consider the possibility of using human vaccines, largely exploited as immune-prophylactics for infectious diseases, as therapeutic tools to prevent or mitigate the expression of cognitive deficits in infectious and chronic degenerative diseases.

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Pamela Rosa-Gonçalves

Papers

Pharmacotherapy of Obesity: Limits and Perspectives.

Malaria Related Neurocognitive Deficits and Behavioral Alterations

Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria

Immunomodulation through vaccination as a promising therapeutic strategy to mitigate malaria-related neurocognitive sequelae

Interplay Between the Immune and Nervous Cognitive Systems in Homeostasis and in Malaria