Weight-reducing Effects Research Articles

Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan.

Treatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach. Seven weeks after initiating a high-fat diet (HFD), C57BL/6N mice received fecal microbiota for 8weeks from donor mice by oral gavage, continuing HFD feeding. Stool samples came from mice that were treated with TEL (8mg/kg/d by gavage, 12weeks), thus remaining lean despite HFD feeding (BL/6>fTEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>fVEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing. Weight gain was lower in BL6>fTEL than in BL6>fVEH mice after 3 but not 8weeks. Energy homeostasis, insulin sensitivity, and body composition did not differ between the two groups. β-diversity indicated group differences (F = 2.27, p = 0.005). Although the Firmicutes/Bacteroides ratio did not differ, abundances of distinct phyla, families, and genera varied. Among others, Ruminococcaceae and Desulfovibrionaceae, Desulfovibrionia uncl., and Lachnospiraceae uncl. were lower in BL/6>fTEL than in BL/6>fVEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>fVEH and negative in BL/6>fTEL mice. As FMT from TEL-pretreated mice influences the microbiota in acceptor mice with slight weight-reducing effects, we confirm the relevance of TEL-related microbiota changes for weight reduction, most likely independent of the transferred stool-residual TEL effect on the host metabolism.

Effects of Krill Oil and Coconut Oil on Behavioral Changes and Inflammatory Markers in Rats with Chronic Unpredictable Mild Stress Induced Depression Model.

This study was conducted to determine the effects of two different types of fat (krill oil [KO] and coconut oil [CO]) on obesity, behavioral tests, and some inflammatory markers when consumed with a high-fat or control diet in rats with depression. The study was conducted mainly in two phases: the induction of depression (37 days) and the dietary intervention (60 days). After the induction of depression by chronic unpredictable mild stress, dietary intervention started. Sixty male Sprague-Dawley rats were divided into 6 groups with 10 rats in each group: (1) standard diet (SD), (2) SD + 5% KO, (3) SD + 5% medium-chain triglyceride (MCT)* (*CO to contain 5% MCT), (4) high-fat diet (HFD), (5) HFD + 5% KO, and (6) HFD + 5% MCT*. The open field test (OFT), forced swimming test (FST), and sucrose preference test were performed at baseline, end of the depression induction, and dietary intervention to observe behavioral changes in rats. After the final behavioral test, animals were sacrificed, and blood samples were collected for biochemical analyses C-reactive protein (milligram per liter), cortisol (microgram per deciliter), and insulin (micro-international units per milliliter) to assess inflammatory changes in the blood. All data were analyzed under two headings: baseline, end of depression induction, end of dietary intervention, and dietary intervention groups. Body weight gain was highest in the SD+KO and lowest in the SD+MCT group (P < .05). When behavioral tests were evaluated according to dietary intervention, it was found that the SD+MCT group spent the most time in the center, the least time in the periphery, and the lowest immobilization time (P < .05). In FST, the SD+KO with the highest weight gain was the most immobile group (P < .05). The study indicates that the weight-reducing effects of MCTs resulted in positive behavioral responses, particularly in OFT and FST. Through these properties, MCTs can be used medicinally in the prevention and treatment of behavioral changes due to depression.

Activity of the hypothalamic neuropeptide Y increases in adult and decreases in old rats.

Middle-aged obesity and aging anorexia with muscle loss (sarcopenia) of old people present public health burden. These alterations may appear both in humans and rodents suggesting the role for regulatory alterations. Previously, we demonstrated that biphasic changes in the weight-reducing (catabolic) effects of neuropeptides of the hypothalamus-adipose tissue axis (e.g. leptin) may contribute to both trends. With regard to the anabolic effects of the hypothalamic neuropeptide Y (NPY) inhibited by leptin, we hypothesized non-linear age-related changes with shifts in the opposite directions. We investigated the orexigenic and hypometabolic effects of intracerebroventricularly administered NPY (hyperphagia induced by NPY injection or changes in food intake, body weight, heart rate, body temperature, locomotor activity during a 7-day NPY infusion), the immunoreactivity and gene expression of NPY in the hypothalamic arcuate nucleus of male Wistar rats of five age groups from young to old. The orexigenic/hypometabolic efficacy and the immunoreactivity of NPY increased in middle-aged animals preceding the peak of adiposity observed in aging rats, then decreased preceding anorexia and weight loss in old rats. These shifts may contribute to the development of both age-related obesity and aging anorexia, sarcopenia, and should be considered in future drug development targeting the NPY system.

Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity.

(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with 18F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments.

VERNONIA AMYGDALINA LEAVES INCORPORATION INTO HIGH FAT DIET EXHIBITED HYPOGLYCEMIC, HEPATOPROTECTIVE, AND WEIGHT LOWERING EFFECTS IN MONOSODIUM GLUTAMATE INTOXICATED WISTAR RATS

Background and aims: Insulin resistance (IR) and obesity (Ob) are hallmarks of metabolic syndrome while high-fat diet (HFD) and monosodium glutamate (MSG) consumption have been implicated in both IR and Ob. In current study, hypoglycemic, hepatoprotective, and weight-reducing effects of dietary Vernonia amygdalina (VA) in MSG-intoxicated HFD fed wistar rats was investigated. Methods: Male wistar rats (36) were randomly allocated into six groups of six rats each, each weighing between 150 and 250 grams on average. The animals were given 5%, 10% dietary incorporated VA (VAHFD), and Orlistat 10 mg/kg for 4 weeks after being treated orally with MSG 8000 mg/kg for the first 8 weeks while on HFD. Changes in the experimental animals' weight, liver histology, total protein and albumin concentrations, and fasting blood glucose concentrations were all noted, and the data was analyzed for statistical significance using appropriate techniques. Results: Peak fasting blood glucose concentration was recorded for the MSG-only group at the end of the study period while 10% VAHFD was greater than Orlistat 10 mg/kg in reducing it. Hepatotoxicity was observed in rats fed the HFD or HFD + MSG while the 10% VAHFD was comparable to Orlistat 10 mg/kg in protecting the liver both of which were greater than the 5% VAHFD. The Orlistat group showed a peak reduction in weight gain from week 9 to the end of week 12, followed by the 5% VAHFD &gt; 10% VAHFD. Conclusions: Following co-intoxication with MSG + HFD, dietary VAHFD was effective in managing hyperglycemia, hepatotoxicity, and weight gain, however, there was no additive effect on toxicity from MSG + HFD co-intoxication on the various studied parameters. Peer Review History: Received 4 February 2024; Revised 11 March 2024; Accepted 19 April; Available online 15 May 2024 Academic Editor: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, amaka_mgbahurike@yahoo.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Ahmad Najib, Universitas Muslim Indonesia, Makassar, Indonesia, ahmad.najib@umi.ac.id Dr. Tamer Elhabibi, Suez Canal University, Egypt, tamer_hassan@pharm.suez.edu.eg

The Body weight Reducing Effects of Tirzepatide in People with and without Type 2 Diabetes: A Review on Efficacy and Adverse Effects.

Obesity is becoming more frequent and has several negative health impacts. Recent advances in weight management strategies have primarily resided in pharmaceutical treatments, and the glucagon-like peptide-1 (GLP-1) receptor agonists have shown great potential in terms of body weight reduction in addition to improving glycemic control in patients with type 2 diabetes (T2D). Recently, the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide has been developed. Tirzepatide has shown strong effects on glycated hemoglobin (HbA1C) levels in several clinical trials including participants with T2D (SURPASS program). In addition to its lowering effect on HbA1C, tirzepatide leads to substantial reductions in body weight, and a series of clinical trials (SURMOUNT program) have investigated the effects on body weight as the primary outcome. In these two trial programs, tirzepatide in doses of 5 mg to 15 mg administered subcutaneously once weekly resulted in body weight reduction of up to 15% in participants with T2D and up to 21% in participants without T2D, despite comparable baseline bodyweight. Across the two trial programs, adverse effects were mainly gastrointestinal (nausea, diarrhea, and vomiting) occurring with similar incidences of vomiting and lower incidences of diarrhea and nausea in trial participants with T2D compared to trials participants without T2D. Overall, discontinuation due to adverse events occurred in 3-7% of participants with no major differences between individuals with and without T2D. The higher weight-reducing efficacy of tirzepatide in trial participants without T2D is currently unexplained and may be partly reflected in dissimilarities in frequencies of gastrointestinal adverse events. The weight reducing effects of tirzepatide hold great promise for weight management in obese patients regardless of the presence of T2D.

Novel GLP-1(28–36) amide-derived hybrid peptide A3 with weight loss and hypoglycemic activities

Glucagon-like peptide-1 (GLP-1) has gained much attention in the last decade for the treatment of type 2 diabetes. Accumulating evidence indicates that some metabolites of GLP-1 have biological activities that might contribute to the pleiotropic effects of GLP-1 independent of the GLP-1 receptor. The hypoglycemic and weight-reducing effects of the reported metabolites and modifications still need to be confirmed. In this study, we started from the C-terminal nonapeptide GLP-1(28–36) amide and developed a series of GLP-1(28–36) amide-derived hybrid peptides. Our findings of biological activity evaluation in INS-1 cells, streptozotocin-induced diabetic and diet-induced obesity mice confirmed a novel hybrid peptide, A3, and provided a new perspective in the development of new drugs from peptide metabolites.

Effect of combined administration of Acyl-CoA: Cholesterol acyltransferase 1 inhibitor and glucagon-like peptide 1 receptor agonist on a rodent model of diet-induced obesity

A glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide was approved for the treatment of obesity by the Food and Drug Administration. However, it can cause gastrointestinal events at high doses, limiting its broader use. Combining drugs with multiple mechanisms of action could enhance the weight-reducing effects while minimizing side effects. To this end, we investigated the combined effects of semaglutide and avasimibe, an acyl-CoA:cholesterol acyltransferase 1 (ACAT1) inhibitor, on weight reduction in diet-induced obesity mice. Two cohorts of mice were used: In cohort 1, mice were fed a high-fat (HF) diet for 12 weeks and then randomly assigned to the vehicle, avasimibe [10 mg/kg body weight (BW)], semaglutide (0.4 mg/kg BW), or combination groups. The drugs were administered via subcutaneous (sc) injections on a daily basis. In cohort 2, mice were fed an HF diet for 8 weeks and randomly assigned to the same four groups, but avasimibe was administered at a dose of 20 mg/kg BW, and the drugs were administered every 3 days. In cohort 1, semaglutide initially reduced food intake initially, but this effect was diminished with prolonged administration. Avasimibe, on the other hand, did not affect food intake but prevented weight gain to a lesser extent than semaglutide. Importantly, the combination treatment resulted in the greatest percentage of body weight reduction, along with lower plasma glucose and leptin levels compared to the semaglutide single-treatment group. Cohort 2 confirmed that the superior weight loss in the combination group compared to the other three groups was largely due to a significant reduction in fat mass. Histological analysis of inguinal adipose tissue showed smaller adipocyte size across all treatment groups compared to the vehicle group, with no significant differences among the treatment groups. Collectively, these findings suggest combining semaglutide and avasimibe could be an effective approach to weight management.

Leptin signaling and its central role in energy homeostasis.

Leptin plays a critical role in regulating appetite, energy expenditure and body weight, making it a key factor in maintaining a healthy balance. Despite numerous efforts to develop therapeutic interventions targeting leptin signaling, their effectiveness has been limited, underscoring the importance of gaining a better understanding of the mechanisms through which leptin exerts its functions. While the hypothalamus is widely recognized as the primary site responsible for the appetite-suppressing and weight-reducing effects of leptin, other brain regions have also been increasingly investigated for their involvement in mediating leptin's action. In this review, we summarize leptin signaling pathways and the neural networks that mediate the effects of leptin, with a specific emphasis on energy homeostasis.

Evaluating probiotic efficacy on weight loss in adults with overweight through a double-blind, placebo-controlled randomized trial

The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month double-blinded, randomized, placebo-controlled trial, followed by a 3-month open phase, was conducted at Karolinska Institutet, Sweden. The probiotic compound AB001 was tested at two doses (single and double) and compared with placebo during the blinded phase, and at triple dose during the open phase. Eighty-one volunteers, 18–45 years old, with overweight were included. The primary outcome was change in weight. Secondary outcomes were changes in; BMI, waist circumference, blood pressure, blood lipids, glucose metabolism, liver enzymes, vitamin levels, and bowel habits. After 3 months (n = 81), no difference in weight, BMI, waist circumference, blood pressure, or biomarkers were observed between the groups. Forty-five individuals continued with triple dose. The group with initial single dose decreased 0.93 ± 4.73 kg (p = 0.34), and the group with double dose initially decreased 1.93 ± 3.70 kg (p = 0.027). Reported changes in bowel habits and gastro-intestinal problems were similar for all doses. The results indicate that a long-term use of at least double dose AB001 may be more beneficial for weight loss than lower doses. However, in the double blinded phase, no differences between groups were found. The probiotic compound AB001 was well tolerated and can safely be used up to double dose for 90 days followed by triple dose for 90 days.Trial registration: Clinicaltrial.gov NCT04897698, registered on 21 May 2021.

Phytochemical analysis, in vitro and in silico effects from Alstonia boonei De Wild stem bark on selected digestive enzymes and adipogenesis in 3T3-L1 preadipocytes

BackgroundObesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body weight reducing effect in obese rats. Thus, this study sought to investigate the in vitro and in silico effects of fractions from Alstonia boonei stem bark on selected obesity-related digestive enzymes and adipogenesis in 3T3-L1 preadipocytes.MethodTwo fractions were prepared from A. boonei: crude alkaloid fraction (CAF) and crude saponin fraction (CSF), and their phytochemical compounds were profiled using Liquid chromatography with tandem mass spectrometry (LCMS/MS). The fractions were assayed for inhibitory activity against lipase, α-amylase and α-glucosidase, likewise their antiadipogenic effect in 3T3-L1 adipocytes. The binding properties with the 3 enzymes were also assessed using in silico tools.ResultsEleven alkaloids and six saponin phytochemical compounds were identified in the CAF and CSF using LCMS/MS. The CAF and CSF revealed good inhibitory activity against pancreatic lipase enzyme, but weak and good activity against amylase respectively while only CSF had inhibitory activity against α-glucosidase. Both fractions showed antiadipogenic effect in the clearance of adipocytes and reduction of lipid content in 3T3-L1 adipocytes. The LCMS/MS identified compounds (41) from both fractions demonstrated good binding properties with the 3 enzymes, with at least the top ten compounds having higher binding energies than the reference inhibitors (acarbose and orlistat). The best two docked compounds to the three enzymes were firmly anchored in the substrate binding pockets of the enzymes. In a similar binding pattern as the reference acarbose, Estradiol-17-phenylpropionate (-11.0 kcal/mol) and 3α-O-trans-Feruloyl-2 α -hydroxy-12-ursen-28-oic acid (-10.0 kcal/mol) interacted with Asp197 a catalytic nucleophile of pancreatic amylase. Estradiol-17-phenylpropionate (-10.8 kcal/mol) and 10-Hydroxyyohimbine (-10.4 kcal/mol) interacted with the catalytic triad (Ser152-Asp176-His263) of pancreatic lipase while Estradiol-17-phenylpropionate (-10.1 kcal/mol) and 10-Hydroxyyohimbine (-9.9 kcal/mol) interacted with Asp616 and Asp518 the acid/base and nucleophilic residues of modelled α-glucosidase.ConclusionThe antiobesity effect of A. boonei was displayed by both the alkaloid and saponin fractions of the plant via inhibition of pancreatic lipase and adipogenesis.

Effect on Hemoglobin A1c (HbA1c) and Body Weight After Discontinuation of Tirzepatide, a Novel Glucose-Dependent Insulinotropic Peptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist: A Single-Center Case Series Study.

Introduction The purpose of this study was to examine changes in blood glucose levels and body weight after discontinuation of tirzepatide, a novel long-acting dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). Methods Nine subjects (five males, four females, age 54.3±5.4 years, body mass index 33.5±3.3 kg/m2) participating with type 2 diabetes in the SURPASS J-mono study were included. Subjects were randomized to tirzepatide 5 mg, 10 mg, 15 mg, or a dulaglutide 0.75 mg group. Fifty-two weeks after randomization, study drug administration was discontinued. To investigate progress after the end of administration, changes in hemoglobin A1c (HbA1c) and body weight were further examined two, four, and six months after discontinuation of the study drug. Results After fifty-two weeks, all tirzepatide groups had improved HbA1c and body weight compared with the dulaglutide group. At two, four, and six months after the end of study drug administration, re-elevation of HbA1c was observed in all groups. Furthermore, in the tirzepatide groups, dose-dependent weight regain was observed from an early stage. Conclusions Compared to dulaglutide, tirzepatide exhibited excellent blood-glucose-improving and weight-reducing effects. However, exacerbation of blood glucose and rebound of weight gain occurred relatively early after administration was ended. For type 2 diabetes patients who need weight loss and are prescribed tirzepatide, these findings suggest a necessity for continuous prescription or careful follow-up when stopping.

Weight Reducing Effect of Moringa Oleifera Leaves Against Induced Obesity in Rabbits

Objectives: To study the weight-reducing effect of M. Oleifera Leaves against induced obesity in rabbits. Study Design and Settings: It was an animal study conducted in the Department of Pharmacology, Liaquat National Hospital &amp; Medical College, Karachi. Methodology: The study period was 6 months, and random sampling was done. Twenty four Healthy rabbits of either sex, weighing 1–2 kg and aged 1-3 years, were included in the study. Sick rabbits weighing less than 1 kg or more than 2 kg and aged less than 1 year or more than 3 years were excluded from the study. Results: The weight of Group B animals fed with a high-fat diet (HFD) for 28 days increased significantly from 1.28±0.07 to 1.88 ± 0.17. While the weight of Group C and D rabbits which were fed with M. oleifera extract(300mg/kg and 600mg/kg) along with a HFD for 28 days, increased slightly from 1.38±0.07 to 1.53± 0.08 and from 1.25±0.13 to 1.38± 0.14 respectively. P-value of weight on Day 28 also became significant with a P-value of (0.000), which was (0.176) on Day 0, proving the anti-obesity effects of M. oleifera leaves. Conclusion: In our study, we found out that there was a significant weight-reducing effect of M. oleifera leaves against obesity induced rabbits as well as skin fold thickness was also decreased. This study also indicates that the given dose of M. oleifera leaves extracts are devoid of any side effects

A polysaccharide from Salvia Miltiorrhizae Radix inhibits weight gain of mice with high-fat diet via modulating intestinal bacteria.

Obesity, a global chronic disease, has been recognized as a sever risk of health. In our study, a novel polysaccharide named ARS was isolated and purified from acrial part of Salvia Miltiorrhizae Radix. Our aims to investigate the weight-reducing effect of a polysaccharide from Salvia Miltiorrhizae Radix on mice with high-fat diet. The novel polysaccharide ARS mainly consisted of glucose and galactose with a molar ratio of 0.59: 1.00. We found that the treatment of ARS could inhibit weight gain of mice with high-fat diet via modulating intestinal bacteria. Moreover, we surveyed its mechanism in mice and the gut microbiota sequencing results demonstrated that ARS can reverse or resist high-fat diet induced significant weight gaining or obesity by increasing the diversity of gut microbiota and optimizing the ratio of Firmicutes to Bacteroidetes. Phylum and species analysis of gut microbiota demonstrated that obesity caused by high fat diet was accompanied by significant changes in the microbial communities, but ARS could reverse the disturbance of gut microbiota induced by high fat diet to keep homeostasis. Overall, our findings suggested the new function of ARS in regulating gut microbiota, which provided a theoretical basis for the development of high-quality ARS functional foods and the application of dietary supplements. This article is protected by copyright. All rights reserved.

Effect of Benaglutide on Gut Microbiota and Fecal Metabolites in Patients with Type 2 Diabetes Mellitus.

Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment. Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed. The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide. These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.

Therapeutic Activity of Green Tea Epigallocatechin-3-Gallate on Metabolic Diseases and Non-Alcoholic Fatty Liver Diseases: The Current Updates.

Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases including obesity, type 2 diabetes, cardiovascular and non-alcoholic fatty liver diseases, and their comorbidities. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and is attributed to antioxidant and free radical scavenging activities, and the likelihood of targeting multiple metabolic pathways. It has been shown to exhibit anti-obesity, anti-inflammatory, anti-diabetic, anti-arteriosclerotic, and weight-reducing effects in humans. Worldwide, the incidences of metabolic diseases have been escalating across all age groups in modern society. Therefore, EGCG is being increasingly investigated to address the problems. This review presents the current updates on the effects of EGCG on metabolic diseases, and highlights evidence related to its safety. Collectively, this review brings more evidence for therapeutic application and further studies on EGCG and its derivatives to alleviate metabolic diseases and non-alcoholic fatty liver diseases.

A New Hope for Treating Obesity Pandemic

A new class of drugs is transforming obesity treatment in an unprecedented manner. Scientists are amazed by their potency in the treatment of obesity. Glucagon-like peptide 1 (GLP-1) analogs are a class of medications used to treat type 2 diabetes mellitus. These analogs mimic the action of GLP-1, a hormone released by the intestine in response to food intake. GLP-1 analogs have been extensively studied, and scientists have made several important discoveries about their effects and potential therapeutic applications. GLP-1 analogs have shown significant efficacy in improving glycemic control in patients with type 2 diabetes. They stimulate insulin secretion from pancreatic beta cells, suppress glucagon secretion (which reduces hepatic glucose production), and slow down gastric emptying, leading to reduced postprandial glucose levels. Apart from their controlling glycemic index, GLP-1 analogs are shown to offer cardio-protective, reno-protective, and neuroprotective benefits. However, their most surprising and potent effects have been observed in the context of weight loss. Two drugs from this class, semaglutide, and tripeptide, have shown efficacy in recent clinical trials. Tirzepatide was effective in significantly reducing body weight in about half of the participants in a recent clinical trial. In another trial, semaglutide was able to reduce 20% of the body weight of about one-third of the participants. However, not everyone is benefiting from these medications. There are still significant challenges in determining who will benefit from these medications and to what extent. These challenges are currently being addressed. It has been observed that the new drugs work best in people who become hungry in between meals. People with obesity can be classified into four categories; those who need to eat more to reach fullness; those who reach fullness with a regular-sized meal but feel hungry again soon (hungry gut); those who eat to cope with emotions; and those with a relatively slow metabolism. It is not known why people with a ‘hungry gut’ respond most effectively to the new drugs, but one hypothesis suggests that these patients have low levels of GLP-1 hormones, and that’s why they have obesity. When they get a replacement in the form of GLP-1 analogs, they do extremely well. Another study with a GLP-1-mimicking drug called liraglutide found that patients with low GLP-1 levels reduced twice as much weight compared to the general population after using the drug for one year. Both semaglutide and tripeptide are given once weekly, thus increasing treatment compliance. Because of their weekly regimen, the drugs will also help people with erratic schedules and work shifts. Some of the other medications have to be taken at a certain time of day, which can be difficult for those with irregular sleep schedules. Another important question is to find out how long these drugs' weight loss benefits remain. One study concluded that semaglutide’s weight-reducing effects last as long as the patients remain on medication. This means that these drugs will be given chronically to obese patients. Whether ‘chronic’ means ‘life-long’ in this context is still to be determined. Perhaps an even more important question that clinicians face is determining how much weight loss is too much, especially when muscle loss is also involved. More research is needed to find a balance where these drugs are used not only for weight reduction but to treat a person for health, prevent disease, and improve quality of life.

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism.

Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin-angiotensin II-aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

Pharmacological Support for the Treatment of Obesity-Present and Future.

Obesity is a growing civilization problem, associated with a number of negative health consequences affecting almost all tissues and organs. Currently, obesity treatment includes lifestyle modifications (including diet and exercise), pharmacologic therapies, and in some clinical situations, bariatric surgery. These treatments seem to be the most effective method supporting the treatment of obesity. However, they are many limitations to the options, both for the practitioners and patients. Often the comorbidities, cost, age of the patient, and even geographic locations may influence the choices. The pharmacotherapy of obesity is a fast-growing market. Currently, we have at our disposal drugs with various mechanisms of action (directly reducing the absorption of calories-orlistat, acting centrally-bupropion with naltrexone, phentermine with topiramate, or multidirectional-liraglutide, dulaglutide, semaglutide). The drugs whose weight-reducing effect is used in the course of the pharmacotherapy of other diseases (e.g., glucose-sodium cotransporter inhibitors, exenatide) are also worth mentioning. The obesity pharmacotherapy is focusing on novel therapeutic agents with improved safety and efficacy profiles. These trends also include an assessment of the usefulness of the weight-reducing properties of the drugs previously used for other diseases. The presented paper is an overview of the studies related to both drugs currently used in the pharmacotherapy of obesity and those undergoing clinical trials, taking into account the individual approach to the patient.

Role of Cinnamon Supplementation on Glycemic Markers, Lipid Profile and Weight Status in Patients with Type II Diabetes

Type II diabetes has been on the rise for the past few decades and the current management plan of diabetes is challenging to individuals in keeping their blood glucose levels within normal limits. There is a constant search of new ways to tackle these challenges. Cinnamon is suggested to have antihyperglycemic and lipid lowering effect and has been proposed to be utilized in type II diabetes. The aim behind this review is to explore the role of cinnamon in improving the glycemic status, lipid profile, and weight status of patients with type II diabetes. PubMed and ScienceDirect databases have been searched for eligible studies conducted until February 2022, the outcomes measured were glycemic markers as primary outcome and lipid profile and weight status as secondary outcomes. A total of ten trials involving 861 patients were included in the study. Five studies have demonstrated reductions in glycemic markers (ranging between −0.56 and −1.9 mmol/L for fasting blood sugar and between −0.21% and −0.93% for glycated hemoglobin) whereas the remaining four did not show any significant reduction. The most improvements in glycemic markers are seen in patients with poorly controlled diabetes and patients with higher body mass index (BMI) values. The majority of the studies did not record improvement in lipid profile. Changes in weight status are only observed in overweight patient category (BMI between 25 and 30). Overall, there is no coherent evidence to decide about antihyperglycemic, lipid lowering, and weight reducing effects of cinnamon in type II diabetes.