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Diabetes, Obesity & Metabolism May 2024There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and... (Meta-Analysis)
Meta-Analysis
There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.
Topics: Adult; Humans; Metformin; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Obesity; Overweight; Weight Loss
PubMed: 38468148
DOI: 10.1111/dom.15501 -
Heliyon Mar 2024The rate of vincristine (VCR) resistance in the treatment of retinoblastoma (RB) is relatively high, and the exact role and mechanism of autophagy and fatty acid (FA)...
The rate of vincristine (VCR) resistance in the treatment of retinoblastoma (RB) is relatively high, and the exact role and mechanism of autophagy and fatty acid (FA) metabolism in RB are still unknown. The aim of this study was to elucidate the molecular mechanism by which acyl-CoA thioesterase 7 (ACOT7) regulates FA metabolism and autophagy, which may lead to potential therapeutic strategies for RB. In the present study, the relationship between FA metabolism and cellular drug sensitivity was evaluated through ACOT7 overexpression or inhibition tests in RB-resistant cells. The lipase inhibitor orlistat and the autophagy inhibitor CQ were used to determine the effects of ACOT7 on FA metabolism, autophagy, and cellular drug sensitivity, as well as the therapeutic value of ACOT7 targeting. The results showed that ACOT7 was upregulated in VCR-resistant RB cells, significantly enhancing cell resistance and indicating that ACOT7 may serve as a biomarker for VCR resistance in RB cells. Knockdown of ACOT7 inhibited FA metabolism and reduced cell viability in VCR-resistant RB cells. The effect of ACOT7 overexpression was opposite to that of ACOT7 knockdown, and ACOT7 overexpression promoted autophagy in VCR-resistant RB cells. After treatment with orlistat or CQ, FA metabolism in VCR-resistant RB cells decreased, cell viability and autophagy were inhibited, EMT was inhibited, and the sensitivity of RB cells to VCR was increased. In conclusion, ACOT7 knockdown can mediate FA metabolism to inhibit autophagy and the migration of RB cells, thereby improving the sensitivity of RB cells to VCR.
PubMed: 38463820
DOI: 10.1016/j.heliyon.2024.e27156 -
Irish Journal of Medical Science Mar 2024Recent guidelines, supported by large, well-designed studies, suggest that bariatric surgery is a safe and effective treatment for adolescents living with severe obesity...
BACKGROUND
Recent guidelines, supported by large, well-designed studies, suggest that bariatric surgery is a safe and effective treatment for adolescents living with severe obesity to improve health and psychosocial functioning. The aim of this study was to assess the opinions and referral practices of general practitioners (GPs) and paediatricians in Ireland.
METHODS
A cross-sectional survey was circulated online to practising paediatricians and GPs. The survey consisted of a short introduction about childhood obesity and 12 questions on adolescent bariatric surgery and obesity medications.
RESULTS
There were 45 unique responses to the survey from 22 GPs (48%), 8 paediatricians (17%), and 15 others. Most GPs (72%) would not consider referring an adolescent for bariatric surgery. Paediatricians were significantly more likely to refer (72% vs. 28%, p = 0.034). A minimum BMI of 40 kg/m was the most common response, which GPs (45%) and paediatricians (37.5%) suggested should be a pre-requisite for surgery. There was strong support for family psychological assessment and a reported deficit in the community support needed to manage obesity. GPs were more likely than paediatricians to respond that anti-obesity medications should be made available to adolescents, specifically liraglutide (45% vs. 25%), semaglutide (45% vs. 37.5%), and orlistat (22% vs. 0%).
DISCUSSION
There is a reluctance among GPs to refer adolescents with severe obesity for consideration of bariatric surgery. Concerns regarding the different obesity treatments held by medical professionals should be addressed through education and engagement and should be fundamental to the development of child and adolescent obesity services.
PubMed: 38459246
DOI: 10.1007/s11845-024-03624-6 -
Frontiers in Microbiology 2024The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels,...
INTRODUCTION
The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels.
METHODS
In this study, 36 yaks were randomly assigned to three groups ( = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration).
RESULTS
16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed_species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group ( < 0.05). At the genus level, the relative abundance of in the HP group was notably greater than that in the LP and MP groups ( < 0.05). Conversely, the relative abundance of displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group ( < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group ( < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group ( < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group ( < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of was negatively correlated with Orlistat concentration; the relative abundance of was positively correlated with D-(-)-Glutamine and L-arginine concentrations.
DISCUSSION
Our findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels.
PubMed: 38419639
DOI: 10.3389/fmicb.2024.1275865 -
Diabetes, Obesity & Metabolism Jun 2024To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022.
AIMS
To describe trends in the use of anti-obesity drugs in Norway during the period 2004-2022.
MATERIALS AND METHODS
We assessed the annual utilization of any available drug indicated for obesity recorded in the nationwide Norwegian Prescribed Drug Register for adults (age 18-79 years) from 1 January 2004 to 31 December 2022. Prevalence was stratified by sex and age group (18-29 years and 10-year age groups thereafter). Additional analyses were performed in individuals initiating treatment with an anti-obesity drug and on the cost of the anti-obesity drugs since 2017.
RESULTS
The prevalence of anti-obesity drug use decreased from 2009, when sibutramine and rimonabant were withdrawn from the market, and increased again after the approval of bupropion-naltrexone in 2017 and liraglutide in 2018. The use of the peripheral-acting anti-obesity drug orlistat decreased from 2004. In 2022, 1.04% of the adult Norwegian population (72.8% women) filled at least one prescription of bupropion-naltrexone, 0.91% used liraglutide (Saxenda; 74.2% women), and semaglutide without reimbursement was used by 0.68% (76.7% women). The prevalence increased with age, peaking in the age group 50 to 59 years, and decreased in older age groups. From 2017 to 2022, 2.8% of the adult residents initiated treatment with an anti-obesity drug. The total sale of those drugs increased from 1.1 million euros in 2017 to 91.8 million euros in 2022.
CONCLUSIONS
The use of anti-obesity drugs in Norway has increased substantially in recent years, especially among women aged 40 to 59 years. Changes in availability and reimbursement have influenced the use of these drugs in recent years.
Topics: Humans; Adult; Norway; Middle Aged; Female; Male; Anti-Obesity Agents; Obesity; Adolescent; Aged; Young Adult; Liraglutide; Bupropion; Naltrexone; Orlistat; Rimonabant; Glucagon-Like Peptides; Drug Costs; Registries; Prevalence; Drug Utilization; Cyclobutanes
PubMed: 38419410
DOI: 10.1111/dom.15515 -
Cells Feb 2024The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption...
The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.
Topics: Humans; Lipogenesis; Sebaceous Glands; Acne Vulgaris; Ethanol; Adenosine Triphosphate
PubMed: 38391942
DOI: 10.3390/cells13040328 -
Journal of Advanced Veterinary and... Dec 2023Various disease complications are a risk of overweight or obesity, so losing weight can reduce the risk of diseases caused by obesity. Binahong leaf ethanol extract ()...
OBJECTIVE
Various disease complications are a risk of overweight or obesity, so losing weight can reduce the risk of diseases caused by obesity. Binahong leaf ethanol extract () is a weight-loss herbal preparation.
AIM
This study aims to analyze whether extract is effective in losing weight by affecting the mechanism of adipogenesis in an animal obesity model.
MATERIALS AND METHODS
Animals were grouped into six groups as follows: the normal diet (K1), the negative control group (K2), the positive control group with Orlistat at a dose of 20 mg/kg BW (K3), an ethanol extract of leaves at doses of 50 mg/kg BW (P1), 100 mg/kg BW group (P2), and 150 mg/kg BW (P3). All rats were fed a diet that consisted of high fat for eight weeks, except K1. Afterward, the treatments were given based on group distribution. Then, the rats were treated based on their groups for 4 weeks, and the high-fat diet was still given during the treatment for the control groups (K2). Anthropometric examinations such as body weight, length, and the circumference of the abdomen were measured. Metabolic parameters, including blood glucose, cholesterol levels, triglyceride levels, and abdominal fat weight, were measured using molecular parameters that measured PI3K levels and Extracellular signal-regulated kinase (ERK) in abdominal fat tissue samples using the ELISA method.
RESULTS
ERK levels of abdominal fat were lowered in the treatment group using the extract of (50 mg/kg BW (P1) and 100 mg/kg BW (P2)) compared to the control group that was given a high-fat diet without treatment. The control group, which was fed a high-fat diet without treatment, had an average ERK level of 10.17 ± 2.98 ng/ml, P1 (50 mg/kg BW). Furthermore, when ethanol extracts were used as opposed to the control group, which received a high-fat diet without treatment, there was an increase in phosphoinositide three-kinase (PI3K) levels (K2). The control group received 9.35 ± 2.87 ng/ml, the treatment group received 100 mg/kg BW (P2) 9.48 ± 1.54 ng/ml, and the treatment group received 150 mg/kg BW (P3) 7.87 ± 1.79 ng/ml. The weight of fat in the abdomen differed between the groups that received a high-fat diet without treatment (K2) and those that received a high-fat diet with treatment (P1, P2, P3; < 0.05).
CONCLUSION
extract possesses anti-obesity activities by decreasing ERK and increasing PI3K levels, as well as reducing abdominal fat weight.
PubMed: 38370901
DOI: 10.5455/javar.2023.j737 -
MSMR Jan 2024The U.S. military has witnessed rising obesity among active component service members. The Department of Defense authorized coverage of weight loss medications in 2018,...
The U.S. military has witnessed rising obesity among active component service members. The Department of Defense authorized coverage of weight loss medications in 2018, but no study has evaluated prescription prevalence within the active component. This descriptive retrospective cohort study analyzed data from active component U.S. military service members from January 2018 through June 2023. The study used data from the Defense Medical Surveillance System to determine prescription period prevalence of weight loss medication. Data on demographics, body mass index, and history of diabetes were considered. The study revealed a 100-fold increase in the prescription period prevalence of weight loss agents in the active component from their initial authorization date. Demographics associated with higher prescription period prevalence were non-Hispanic Black race and ethnicity, female sex, and older age. Service members in the health care occupations and the Navy had higher prevalence compared to other service branches and occupations. The findings indicate a significant rise in the period prevalence of weight loss prescriptions over time. Further research is recommended to assess the effectiveness, safety, and use in austere military environments.
Topics: Female; Humans; United States; Prevalence; Retrospective Studies; Military Personnel; Anti-Obesity Agents; Weight Loss
PubMed: 38359359
DOI: No ID Found -
Obesity Reviews : An Official Journal... May 2024This systematic review and meta-analysis evaluated the efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic ovary syndrome (PCOS) to inform the 2023 update of the International Evidence-based Guideline on PCOS. We searched Medline, EMBASE, PsycInfo, and CINAHL until July 2022 with a 10-year limit to focus on newer agents. Eleven trials (545 and 451 participants in intervention and control arms respectively, 12 comparisons) were included. On descriptive analyses, most agents improved anthropometric outcomes; liraglutide, semaglutide and orlistat appeared superior to placebo for anthropometric outcomes. Meta-analyses were possible for two comparisons (exenatide vs. metformin and orlistat + combined oral contraceptive pill [COCP] vs. COCP alone). On meta-analysis, no differences were identified between exenatide versus metformin for anthropometric, biochemical hyperandrogenism, and metabolic outcomes, other than lower fasting blood glucose more with metformin than exenatide (MD: 0.10 mmol/L, CI 0.02-0.17, I = 18%, 2 trials). Orlistat + COCP did not improve metabolic outcomes compared with COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I = 67%, 2 trials). Published data examining the effects of anti-obesity agents in women with PCOS are very limited. The role of these agents in PCOS should be a high priority for future research.
Topics: Female; Humans; Polycystic Ovary Syndrome; Anti-Obesity Agents; Contraceptives, Oral, Combined; Orlistat; Exenatide; Metformin; Hypoglycemic Agents
PubMed: 38355887
DOI: 10.1111/obr.13704