Rising rates of obesity has increased the global use of herbal supplements intended to control weight. However, taking these preparations without appropriate medical supervision could increase the risk of manifestation of side effects, especially at the hepatic level. In literature, different cases of acute liver injury consequent to the use of food supplements containing Garcinia cambogia and hydroxycitric acid are reported. This letter aims to review the most recent literature that analysed the herb-induced liver disease due to the use of hydroxycitric acid, from the first alert coming from the European Food and Drug Administration in 2009, to the last recent European food alerts from 2020 to 2021. It is noteworthy that in some cases it demonstrated the relationship between hydroxycitric acid and hepatotoxicity. Therefore, there is a need to draw more attention to the relationship between a safe use and a more awareness in the intake of these supplements, to preserve the safety of the consumers who increasingly purchase food supplements, products that have only nutritive properties and are never curative.
Anti-Obesity Agents/pharmacology* ; Chemical and Drug Induced Liver Injury/etiology* ; Citrates ; Dietary Supplements/adverse effects* ; Humans ; Plant Extracts/pharmacology*

Tripterygium hypoglaucum (Levl.) Hutch, a traditional Chinese medicinal herb with a long history of use, is widely distributed in China. One of its main active components, celastrol, has great potential to be developed into anti-cancer and anti-obesity drugs. Although it exhibits strong pharmacological activities, there is a lack of sustainable sources of celastrol and its derivatives, making it crucial to develop novel sources of these drugs through synthetic biology. The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases. Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases (CYP450s). Here, we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast. Through substrate supplementation and in vitro enzyme analysis, ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid, which is considered a vital step in the biosynthesis of celastrol, and will lay a foundation for further analysis of its biosynthetic pathway.
Anti-Obesity Agents ; Cytochrome P-450 Enzyme System/metabolism* ; Pentacyclic Triterpenes ; Squalene/analogs & derivatives* ; Tripterygium/metabolism* ; Triterpenes/metabolism*

Objective: To analyze the incidence of early severe complications following bariatric and metabolic surgery and the experience of their diagnosis, treatment, and risk factors. Methods: In this retrospective observational study, the clinical data of 4255 patients who underwent bariatric and metabolic surgery between May 2010 and May 2022 in the Department of Bariatric and Metabolic Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. Among these patients, 1125 were male and 3130 were female. The mean age and body mass index (BMI) of the patients at the time of operation were 31.3±4.5 years and 36.5±6.4 kg/m², respectively. Regarding surgical type, 2397 patients underwent sleeve gastrectomy (SG), 489 underwent Roux-en-Y gastric bypass (RYGB), 1028 underwent sleeve gastrectomy plus jejunojejunal bypass (SG+JJB), and 341 underwent single anastomosis duodenal switch (SADS). The inclusion criteria were patients (1) with a Clavien-Dindo grade of ≥III; (2) who were undergoing SG, RYGB, SG-JJB, or SADS; and (3) who had complete clinical data. The exclusion criteria were patients (1) undergoing revisional surgery and (2) other operations during the bariatric and metabolic surgery. The Clavien-Dindo classification was used to analyze the incidence of early severe postoperative complications and their prognosis. Early severe postoperative complications were defined as Clavien-Dindo ≥ III complications within 30 days after surgery. Meanwhile, multivariate logistic regression model was used to identify risk factors of the complications. Results: Summary of early severe complications following bariatric and metabolic surgery: (1) of the 4255 patients, 22 (12 male and 10 female) exhibited early severe complications (0.52%). The mean age and BMI of these patients were 41.1±9.9 years and 36.9±8.2 kg/m², respectively. Preoperatively, 7 patients had hypertension, 10 had type 2 diabetes mellitus, 1 had respiratory failure, and 1 had heart failure. The severe complications included 9 patients (0.21%) with grade IIIa, 11 (0.26%) with grade IIIb, 1 (0.02%) with grade IVa, and 1 (0.02%) with grade V complications. The incidences of severe postoperative complications in the different surgical procedures were 0.17% for SG (4/2397), 0.61% for RYGB (3/489), 0.58% for SG+JJB (6/1028), and 2.64% for SADS (9/341). The common severe complications were leakage (0.28%, 12 patients), bleeding (0.14%, 6 patients), and obstruction (0.05%, 2 patients). (2) Management of complications: Grade IIIa complications (including eight patients with leakage and one with severe inflammation) were treated with antibiotics, nasogastric and nutritional tube placements, and CT-guided drainage. For grade IIIa complications, five patients with bleeding were treated with reoperation, and all the patients recovered; four patients with leakage were treated with reoperation, wherein three were converted to RYGB and one patient underwent resuturing of the leakage site; two patients with obstruction were treated with adhesiolysis. The patient with grade IVa complication (including respiratory failure complicated with acid aspiration) was treated in the ICU. For the grade V complication, bleeding in a patient with SG+JJB was treated with reoperation, which confirmed the bleeding of short gastric vessels. Unfortunately, the patient died. (3) Risk factor analysis of early severe complications: univariate analysis detected that sex, age, type 2 diabetes mellitus, operation time, and surgical type were associated with postoperative complications (P<0.05). However, multivariate analysis indicated that an age of ≥31.3 years (odds ratio [OR] = 5.423, 95% confidence interval [CI]: 1.004-29.278, P=0.049) and surgical type (SADS: OR = 19.758, 95%CI: 5.803-67.282, P<0.001; RYGB: OR = 9.752, 95%CI: 2.456-38.723, P=0.001; SG+JJB: OR = 5.706, 95%CI: 1.966- 16.559, P=0.001) were independent risk factors of early severe complications following bariatric and metabolic surgery. Conclusion: Bariatric and metabolic surgery is safe. Its common postoperative complications include leakage, bleeding, and obstruction, which require early detection, diagnosis, and treatment to improve treatment outcomes. Age and surgical type are independent risk factors of early severe complications following bariatric and metabolic surgery.
Adult ; Anti-Bacterial Agents ; Bariatric Surgery/adverse effects* ; Diabetes Mellitus, Type 2/surgery* ; Female ; Gastrectomy/methods* ; Gastric Bypass/adverse effects* ; Humans ; Male ; Obesity, Morbid/surgery* ; Postoperative Complications/epidemiology* ; Respiratory Insufficiency/etiology* ; Retrospective Studies ; Risk Factors ; Treatment Outcome

Objective: To investigate the potential independent risk factors of body mass rebound following laparoscopic sleeve gastrectomy (LSG) and construct a nomogram prediction model based on these factors. Methods: In this retrospective observational study, patients with obesity who had undergone LSG at the Department of Gastrointestinal Surgery of the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University between January 2015 and July 2017 were retrospectively enrolled. These patients were divided according to their status of postoperative body mass rebound. The inclusion criteria were patients aged between 16 and 65 years who had undergone LSG bariatric surgery with surgical indications according to the 2014 Chinese Guidelines for the Surgical Management of Obesity and Type 2 Diabetes Mellitus. The exclusion criteria were patients who had undergone other bariatric surgeries, who were taking weight-loss drugs or drugs that affected their body weight, who had severe gastroesophageal reflux and hiatal hernia, who were pregnant, who had incomplete clinical data, and who were lost to follow-up or were followed up for <3 years. In total, 241 patients with obesity (69 males and 172 females) who had undergone LSG surgery were enrolled. The mean age and body mass index (BMI) were (29.9±5.8) years and (40.8±4.8) kg/m², respectively. The patients were followed up till July 2022, with a focus on their body weight. Postoperative body mass rebound was defined as a percentage increase of ≥10% from the nadir body mass, which was the lowest body mass during the 3-year follow-up period. The body weight rebound following LSG and its influencing factors were observed, based on which a nomogram model was constructed and evaluated. The relationships between the patients' basic data, clinical indicators, preoperative hematological indicators, postoperative indicators, and body weight rebound following LSG were analyzed via univariate analysis. Independent risk factors were further screened by multivariate logistic regression analysis. Factors with a statistically significant difference were included into the nomogram prediction model. Moreover, the model was internally (modeling set) and externally (validation set, 80 baseline data-matched patients with obesity from our center) validated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) via R software. ROC curve analysis was used to analyze the predictive and cutoff values of the measurement data for body mass rebound. Results: Overall, 90 patients (37.3%) exhibited postoperative body weight rebound, with the lowest BMI of (29.5±2.6) kg/m² and time to reach the lowest BMI of (15.4±2.3) months; 151 patients (62.7%) did not exhibit body weight rebound, with the lowest BMI of (29.8±2.3) kg/m² and time to reach the lowest BMI of (14.7±2.1) months. The results of univariate analysis showed that BMI, depression, anxiety, C-reactive protein (CRP) levels, systemic immune inflammatory index (SII), prognostic nutritional index (PNI), and albumin/fibrinogen ratio (AFR) were associated with body weight rebound following LSG with statistically significant differences (all P<0.05). The results of multivariate regression analyses suggested that depression [odds ration (OR) = 1.31, 95% confidence interval (CI): 1.08-1.62, P=0.010], preoperative CRP levels of ≥8 mg/L (OR = 1.34, 95% CI: 1.09-1.69, P=0.007), SII (OR = 0.58, 95% CI: 0.41-0.86, P=0.013), PNI (OR = 2.06, 95% CI: 1.03-4.21, P=0.007), and AFR (OR: 0.49, 95% CI: 0.33-0.69, P=0.011) were five independent risk factors for body mass rebound. A nomogram prediction model was constructed based on the multivariate analysis results. The scores of PNI, SII, AFR, CRP, and depression were 92.5, 100, 72.5, 25, and 27.5, respectively. The total score was calculated by adding the individual scores of each risk factor, which was used to calculate the probability of body mass rebound following LSG. The evaluation results of the nomogram model showed a C-index of 0.713 and 0.762, sensitivity of 0.656 and 0.594, and specificity of 0.715 and 0.909 in the modeling and validation sets, respectively. The calibration curve analysis and DCA indicated that the nomogram model has a good predictive value for body mass rebound after LSG. Conclusion: Preoperative depression, CRP of ≥8 mg/L, SII, PNI, and AFR were independent risk factors for body mass rebound following LSG. Hence, the nomogram prediction model based on these factors can effectively predict body mass rebound in patients undergoing LSG.
Adolescent ; Adult ; Aged ; Anti-Obesity Agents ; C-Reactive Protein ; Diabetes Mellitus, Type 2 ; Factor Analysis, Statistical ; Female ; Fibrinogen ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Middle Aged ; Nomograms ; Obesity ; Retrospective Studies ; Risk Factors ; Weight Loss ; Young Adult

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.
3T3 Cells ; Adipocytes ; drug effects ; physiology ; Adipose Tissue, Brown ; drug effects ; physiology ; Adipose Tissue, White ; drug effects ; physiology ; Animal Feed ; analysis ; Animals ; Anti-Obesity Agents ; administration & dosage ; metabolism ; Cell Differentiation ; drug effects ; Diet ; Fermentation ; Hordeum ; chemistry ; Lactobacillus plantarum ; chemistry ; Male ; Mice ; Obesity ; drug therapy ; genetics ; Plant Extracts ; chemistry ; Probiotics ; administration & dosage ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uncoupling Protein 1 ; genetics ; metabolism

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.
Anti-Obesity Agents ; Bariatric Surgery ; Bupropion ; Dopamine ; Glucagon-Like Peptide-1 Receptor ; Humans ; Korea ; Liraglutide ; Naltrexone ; National Health Programs ; Neurons ; Neuropeptide Y ; Obesity ; Pro-Opiomelanocortin ; Reward

Penile prosthesis infection is the most significant complication following prosthesis implant surgery leading to postoperative morbidity, increased health care costs, and psychological stress for the patient. We aimed to identify risk factors associated with increased postoperative penile prosthesis infection. A review of the literature was performed via PubMed using search terms including inflatable penile prosthesis, penile implant, and infection. Articles were given a level of evidence score using the 2011 Oxford Centre for Evidence-Based Medicine Guidelines. Multiple factors were associated with increased risk of post-prosthesis placement infection (Level of Evidence Rating) including smoking tobacco (Level 1), CD4 T-cell count <300 (Level 4), Staphylococcus aureus nasal carriage (Level 2), revision surgery (Level 2), prior spinal cord injury (Level 3), and hemoglobin A1c level >8.5 (Level 2). Factors with no effect on infection rate include: preoperative cleansing with antiseptic (Level 4), history of prior radiation (Level 3), history of urinary diversion (Level 4), obesity (Level 3), concomitant circumcision (Level 3), immunosuppression (Level 4), age >75 (Level 4), type of hand cleansing (Level 1), post-surgical drain placement (Level 3), and surgical approach (Level 4). Factors associated with decreased rates of infection included: surgeon experience (Level 2), “No Touch” technique (Level 3), preoperative parenteral antibiotics (Level 2), antibiotic coated devices (Level 2), and operative field hair removal with clippers (Level 1). Optimization of pre-surgical and intraoperative risk factors is imperative to reduce the rate of postoperative penile prosthesis infection. Additional research is needed to elucidate risk factors and maximize benefit.
Anti-Bacterial Agents ; Erectile Dysfunction ; Evidence-Based Medicine ; Hair Removal ; Hand ; Health Care Costs ; Humans ; Immunosuppression ; Male ; Obesity ; Penile Prosthesis ; Prostheses and Implants ; Risk Factors ; Sexual Dysfunction, Physiological ; Smoke ; Smoking ; Spinal Cord Injuries ; Staphylococcus aureus ; Stress, Psychological ; T-Lymphocytes ; Tobacco ; Urinary Diversion

Recently, the number of obesity and diabetes mellitus have increased rapidly not only in Korea but also around the world. It is even called the new pandemic of the 21st century. In Korea, the diabetes growth rate, which exceeds the obesity growth rate, is a bigger problem. Accordingly, the simultaneous treatment of diabetes and obesity has become a global issue. In this article, we will review various obesity treatments to help diabetes remission and take a look at meaningful previous study about dietary methods for obesity. This overview includes the update of medications for obesity and the practical method for clinicians in field of obesity treatment in Korea.
Anti-Obesity Agents ; Diabetes Mellitus ; Diet Therapy ; Korea ; Methods ; Obesity ; Pandemics

Over the last 5 years, the Korean Ministry of Food and Drug Safety has approved four anti-obesity drugs for long-term weight management. In this review, the mechanisms of action and clinical applications of lorcaserin, naltrexone/bupropion, liraglutide, and phentermine/topiramate have been clarified. Lorcaserin stimulates proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons in the arcuate nucleus. Naltrexone/bupropion reduces body weight by controlling the hedonic reward system of food intake. The hypophagic effect of liraglutide depends on the direct activation of the proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons and indirect suppression of neuropeptide Y/agouti-related peptide neurons through gammaaminobutyric acid-dependent signaling, with an additional thermogenic effect. Phentermine/topiramate induces weight loss by elevating the norepinephrine levels in the hypothalamus, reducing energy deposition in the adipose tissue and skeletal muscle, and elevating the corticotropin-releasing hormone in the hypothalamus. In patients with high cardiovascular risks or type 2 diabetes mellitus, lorcaserin and liraglutide are appropriate. In patients with mood disorders, naltrexone/bupropion could be considered as the first choice of therapy. Notably, lorcaserin and liraglutide are neutral in the aspect of sleep disorder. In case of obese individuals with obstructive sleep apnea, liraglutide or phentermine/topiramate would be selected as the treatment option. These four drugs should be used after considering the patients' co-morbidities of obesity.
Adipose Tissue ; Anti-Obesity Agents ; Arcuate Nucleus of Hypothalamus ; Body Weight ; Corticotropin-Releasing Hormone ; Diabetes Mellitus, Type 2 ; Eating ; Humans ; Hypothalamus ; Korea ; Liraglutide ; Mood Disorders ; Muscle, Skeletal ; Neurons ; Neuropeptides ; Norepinephrine ; Obesity ; Pharmacology ; Reward ; Sleep Apnea, Obstructive ; Sleep Wake Disorders ; Weight Loss

Laparoscopic sleeve gastrectomy has become a standard procedure in bariatric surgery owing to its efficacy and simplicity. However, this procedure can cause life-threatening complications such as a gastric staple-line leak. A 24-year-old woman was transferred to the emergency department for evaluation of epigastric pain. Nine days prior to transfer, she underwent laparoscopic sleeve gastrectomy at another institution. Abdominal computed tomography (CT) revealed fluid collection with air density along the left subphrenic space and gastrosplenic ligament area. Intravenous antibiotics and total parenteral nutrition were initiated. She underwent percutaneous catheter drainage. On postoperative day 18, an esophagogastroduodenoscopy was performed to assess the site and size of the leak, and revealed a leak at the proximal staple line just below the gastroesophageal junction. A newly designed, fully covered antimigratory esophageal stent was placed to cover the leak from the distal esophagus to gastric midbody. Follow-up abdominal CT demonstrated improvement of the fluid collection at the location of the previous gastric leak. The stent was removed 3 weeks after insertion, and a barium study confirmed no more leakage. In this case, we experienced that the newly designed esophageal stent was safe and effective for preventing migration in the management of leak after laparoscopic sleeve gastrectomy.
Anastomotic Leak ; Anti-Bacterial Agents ; Bariatric Surgery ; Barium ; Catheters ; Drainage ; Emergency Service, Hospital ; Endoscopy, Digestive System ; Esophagogastric Junction ; Esophagus ; Female ; Follow-Up Studies ; Gastrectomy ; Humans ; Ligaments ; Obesity ; Parenteral Nutrition, Total ; Stents ; Tomography, X-Ray Computed ; Young Adult