Assessment of Anti-Obesity Activity of Tectona Grandis Leaves on Butter Induced Hyperlipidemia in Mice

Objective: Obesity is one of the world's leading problems, which is major cause of cardiovascular diseases. During COVID-19 pandemic many young children and all age group people are getting challenged by obesity due stagnant life style. To treat such life-threatening disorder natural remedies acquire prior position, plant produces a good deal of secondary metabolites which have a benefited mankind in various ways, including treatment of diseases. The present research work was focused on developing a natural remedy using Tectona grandis, an ancient plant with number of proven activities in traditional medicine. Method(s): In the literature survey, it was found that flavonoids, sterols, tannins, and alkaloids shown promising effects to tackle obesity by various mechanisms, T. grandis has shown the presence of saponins, alkaloids, flavonoids, proteins, and amino acids. With the above evidence, this plant has been selected for screening of its antiobesity activity against high-fat diet induced obesity in mice. Studies were conducted using aqueous extract of T. grandis leaves (AETG) on high-fat diet (butter) induced model of hyperlipidemia in mice. During 21 days' time period AETI low and high doses were induced to respective animal groups along with butter where atorvastatin has been taken as standard drug. Butter enhanced the cholesterol and triglyceride, low-density lipoprotein (LDL) levels. Results and Discussion: At the end of 21 days, blood samples were collected from the animal through retroperitoneal route. Biochemical parameters of AETG have been compared with that of standard drug group of animals. The test results were almost similar and for some particular parameters such as LDL and very low-density lipoprotein, AETG shown good results than standard drug results. Conclusion(s): In congruence with these results, it may be confirmed that due to the presence of phytoconstituents such as saponins, flavonoids, proteins, terpenoids, amino acids, and alkaloids in the aqueous extract of T. grandis, it could be responsible for the observed significant anti-obesity activity. Copyright © 2022 The Authors.

Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction during High-Fat Diet-Induced Obesity.

Obesity is of concern to the population because it is known to cause inflammation and oxidative stress throughout the body, leading to patient predisposition for health conditions such as diabetes, hypertension, and some cancers. However, some proteins that are activated in times of oxidative stress may provide cytoprotective properties. In this study, we aim to gain further understanding of the interconnection between Nrf2 and Sesn2 during obesity-related stress and how this relationship can play a role in cardio-protection. Cardiomyocyte-specific Sesn2 knockout (cSesn2-/-) and Sesn2 overexpressed (tTa-tet-Sesn2) mice and their wildtype littermates (Sesn2flox/flox and tet-Sesn2, respectively) were assigned to either a normal chow (NC) or a high-fat (HF) diet to induce obesity. After 16 weeks of dietary intervention, heart function was evaluated via echocardiography and cardiac tissue was collected for analysis. Immunoblotting, histology, and ROS staining were completed. Human heart samples were obtained via the LifeLink Foundation and were also subjected to analysis. Overall, these results indicated that the overexpression of Sesn2 appears to have cardio-protective effects on the obese heart through the reduction of ROS and fibrosis present in the tissues and in cardiac function. These results were consistent for both mouse and human heart samples. In human samples, there was an increase in Sesn2 and Nrf2 expression in the obese patients' LV tissue. However, there was no observable pattern of Sesn2/Nrf2 expression in mouse LV tissue samples. Further investigation into the link between the Sesn2/Nrf2 pathway and obesity-related oxidative stress is needed.

Reduced DMPC and PMPC in Lung Surfactant Promotes SARS-CoV-2 Infection in Obesity

Background: Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through lungs, where the Spike protein of SARS-CoV-2 binds to ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids especially phosphatidylcholines (PC) and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-disease. Methods: Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. Results: Lipidomic analysis revealed that myristic acid containing dimyristoyl-PC (DMPC) and palmitoylmirystoyl-PC (PMPC) were commonly reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice reduced wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol. Conclusions: The reduced DMPC and PMPC in lung surfactant contributes to the increased SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant may be an innovative strategy for preventing and treating severe COVID-disease in obesity.

Prospects in GSK-3 Signaling: From Cellular Regulation to Disease Therapy

[...]the incorrect regulation of these pathways as a result of GSK-3 hyperactivity impairs normal cellular homeostasis. [...]disruptions to the normal niche function, reflected by GSK-3 hyperactivity, may be used as a diagnostic tool to detect aberrant activity of stem cells [5]. [...]the absence of GSK-3 improved glucose tolerance (GTT) in insulin-resistant animals fed a high-fat diet (HFD), but did not affect their body weight. [...]maintaining a healthy weight is of prime importance for patients on chronic lithium therapy [10].

Anti-Obesity Effects of Ecklonia cava Extract in High-Fat Diet-Induced Obese Rats.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats' models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet.

Partial Replacement of Dietary Fat with Krill Oil or Coconut Oil Alleviates Dyslipidemia by Partly Modulating Lipid Metabolism in Lipopolysaccharide-Injected Rats on a High-Fat Diet.

This study investigated the effects of partial replacement of dietary fat with krill oil (KO) or coconut oil (CO) on dyslipidemia and lipid metabolism in rats fed with a high-fat diet (HFD). Sprague Dawley rats were divided into three groups as follows: HFD, HFD + KO, and HFD + CO. The rats were fed each diet for 10 weeks and then intraperitoneally injected with phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) (1 mg/kg). The KO- and CO-fed rats exhibited lower levels of serum lipids and aspartate aminotransferases than those of the HFD-fed rats. Rats fed with HFD + KO displayed significantly lower hepatic histological scores and hepatic triglyceride (TG) content than rats fed with HFD. The KO supplementation also downregulated the adipogenic gene expression in the liver. When treated with LPS, the HFD + KO and HFD + CO groups reduced the adipocyte size in the epididymal white adipose tissues (EAT) relative to the HFD group. These results suggest that KO and CO could improve lipid metabolism dysfunction.

Diet Impact on Obesity beyond Calories and Trefoil Factor Family 2 (TFF2) as an Illustration: Metabolic Implications and Potential Applications.

Obesity is a health problem with increasing impacts on public health, economy and even social life. In order to reestablish the energy balance, obesity management focuses mainly on two pillars; exercise and diet. Beyond the contribution to the caloric intake, the diet nutrients and composition govern a variety of properties. This includes the energy balance-independent properties and the indirect metabolic effects. Whereas the energy balance-independent properties are close to "pharmacological" effects and include effects such as antioxidant and anti-inflammatory, the indirect metabolic effects represent the contribution a diet can have on energy metabolism beyond the caloric contribution itself, which include the food intake control and metabolic changes. As an illustration, we also described the metabolic implication and hypothetical pathways of the high-fat diet-induced gene Trefoil Factor Family 2. The properties the diet has can have a variety of applications mainly in pharmacology and nutrition and further explore the "pharmacologically" active food towards potential therapeutic applications.

Ketogenic Diet for Obese COVID-19 Patients: Is Respiratory Disease a Contraindication? A Narrative Review of the Literature on Ketogenic Diet and Respiratory Function.

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

Adaptation of fuel selection to acute decrease in voluntary energy expenditure is governed by dietary macronutrient composition in mice.

In humans, exercise-induced thermogenesis is a markedly variable component of total energy expenditure, which had been acutely affected worldwide by COVID-19 pandemic-related lockdowns. We hypothesized that dietary macronutrient composition may affect metabolic adaptation/fuel selection in response to an acute decrease in voluntary activity. Using mice fed short-term high-fat diet (HFD) compared to low-fat diet (LFD)-fed mice, we evaluated whole-body fuel utilization by metabolic cages before and 3 days after omitting a voluntary running wheel in the cage. Short-term (24-48 h) HFD was sufficient to increase energy intake, fat oxidation, and decrease carbohydrate oxidation. Running wheel omission did not change energy intake, but resulted in a significant 50% decrease in total activity and a ~20% in energy expenditure in the active phase (night-time), compared to the period with wheel, irrespective of the dietary composition, resulting in significant weight gain. Yet, while in LFD wheel omission significantly decreased active phase fat oxidation, thereby trending to increase respiratory exchange ratio (RER), in HFD it diminished active phase carbohydrate oxidation. In conclusion, acute decrease in voluntary activity resulted in positive energy balance in mice on both diets, and decreased oxidation of the minor energy (macronutrient) fuel source, demonstrating that dietary macronutrient composition determines fuel utilization choices under conditions of acute changes in energetic demand.

Effect of Soybean and Soybean Koji on Obesity and Dyslipidemia in Rats Fed a High-Fat Diet: A Comparative Study.

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.

Intestinal expression of ACE2 in mice with high-fat diet-induced obesity and neonates exposed to maternal high-fat diet.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) is threatening global health and is especially pronounced in patients with chronic metabolic syndromes. Meanwhile, a significant proportion of patients present with digestive symptoms since angiotensin-converting enzyme 2 (ACE2), which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the intestine. The aim of this study was to evaluate the effects of a high-fat diet (HFD) and a maternal HFD on the intestinal ACE2 levels in adults and neonates. METHODS: We examined intestinal ACE2 protein levels in mice with diet-induced obesity (DIO) and neonatal mice exposed to a maternal HFD. We also investigated Ace2 mRNA expression in intestinal macrophages. RESULTS: Intestinal ACE2 protein levels were increased in DIO mice but decreased in offspring exposed to a maternal HFD compared with chow-fed controls. Ace2 mRNA expression in intestinal macrophages was detected and downregulated in DIO mice. Additionally, higher intestinal ACE2 protein levels were observed in neonates than in adult mice. CONCLUSIONS: The influence of an HFD on intestinal ACE2 protein levels is opposite in adults and neonates. Macrophages might also be involved in SARS-CoV-2 intestinal infection. These findings provide some clues for the outcomes of patients with COVID-19 with metabolic syndromes.

Gut microbiome dysbiosis and endotoxemia - Additional pathophysiological explanation for increased COVID-19 severity in obesity.

The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. What is more, high-fat diet, as well as obesity per se, enhance intestinal permeability through various mechanisms. Latter results in increased paracellular absorption and transcellular (via chylomicrons) transport of endogenous endotoxin in the circulatory system (endotoxemia). In addition, it is known that lipid A initiates a signaling cascade resulting in activation of various proinflammatory pathways and increases oxidative stress upon binding to tool-like receptor 4 (TLR4). Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity.