Changes In Body Weight Research Articles

FADD regulates adipose inflammation, adipogenesis, and adipocyte survival

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.

Public Fear of Pancreatic Diseases: Causes and Clinical Outcomes at a Single Korean Center.

The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals. This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies. The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC. Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.

The Effect of Mobile Lifestyle Intervention Combined with High-Protein Meal Replacement on Liver Function in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Pilot Randomized Controlled Trial

While many studies have explored dietary substitutes and mobile apps separately, a combined approach to metabolic dysfunction-associated steatotic liver disease (MASLD) has not been investigated. This study evaluated short-term mobile interventions coupled with partial meal replacement in patients with MASLD. Sixty adults with MASLD and a body mass index ≥25 kg/m2 from a health examination center were randomized into an intervention group using a mobile app with partial meal replacements or a control group receiving standard educational materials. Liver enzyme levels, lipid profiles, and anthropometric measurements were assessed at baseline and after 4 weeks. Twenty-five participants in the intervention group and 24 in the control group completed the trial. Significant reductions were observed in the intervention group for alanine aminotransferase (−28.32 versus [vs.] −10.67, p = 0.006) and gamma-glutamyl transferase (−27.76 vs. 2.79, p = 0.014). No significant changes in aspartate aminotransferase, body weight, or waist circumference were noted in the intervention group. Four weeks of mobile lifestyle intervention incorporating partial meal replacements improved liver enzyme profiles in patients with MASLD. This strategy demonstrated the potential for mitigating elevated liver enzyme levels without altering body weight or waist circumference. Comprehensive and longer-term research is needed to substantiate and elaborate these preliminary outcomes.

Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD.

Endothelin receptor antagonists (ERAs) reduce albuminuria but are limited by fluid retention risk, particularly in patients with chronic kidney disease (CKD). Combining ERAs with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which have diuretic effects, offers a promising strategy to mitigate fluid retention. In this post-hoc analysis of the ZENITH-CKD trial, we assessed fluid dynamics in patients with CKD treated with the ERA zibotentan alone, and in combination with the SGLT2 inhibitor dapagliflozin. In ZENITH-CKD, 508 patients with CKD (estimated glomerular filtration rate ≥ 20 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 150-5000 mg/g) were randomized to treatment with placebo, dapagliflozin 10 mg plus placebo, zibotentan (0.25, 1.5 or 5 mg) plus dapagliflozin 10 mg and zibotentan 5 mg plus placebo. We evaluated correlations between changes in fluid retention markers and bioimpedance-measured extracellular fluid (ECF) in response to zibotentan treatment. We used Cox proportional hazards regression to assess the association between zibotentan/dapagliflozin treatment, baseline characteristics, and fluid retention, and the relationship between zibotentan plasma exposure and fluid retention. After 3 weeks of treatment with zibotentan 0.25, 1.5 or 5 mg plus dapagliflozin 10 mg, changes in body weight (β=0.36 [95%CI 0.26,0.45]) per kg, B-type natriuretic peptide (β=0.38 [95%CI 0.22, 0.54]) per doubling, and hemoglobin (β=-0.29 [95%CI -0.48, -0.10]) per g/dL were independently associated with changes in ECF. Higher doses of zibotentan were associated with significantly higher risk of fluid retention compared to dapagliflozin alone (zibotentan 5 mg HR 8.50 (95%CI 3.40, 21.30). The hazard ratio attenuated when zibotentan was combined with dapagliflozin (HR zibotentan/dapagliflozin 5/10 mg 3.09 [95%CI 1.08, 8.80], zibotentan/dapagliflozin 1.5/10 mg 2.70 [95%CI 1.44, 5.07] and zibotentan/dapagliflozin 0.25/10 mg HR 1.21 [95%CI 0.50, 2.91]). The risk of fluid retention was higher with higher zibotentan exposure and lower eGFR. High doses of zibotentan were associated with a higher risk of fluid retention, which was attenuated with lower doses and the addition of dapagliflozin.

Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial.

The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. ClinicalTrials.gov NCT04017832. This trial was funded by Novo Nordisk A/S, Søborg, Denmark.

Micromassage Compression Leggings Associated with Physical Exercise: Pilot Study and Example of Evaluation of the Clinical and Instrumental Effectiveness of Conservative Treatment in Lipedema

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi–Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

A New Alternative Nutritional Source Hawthorn Vinegar: How It Interacts with Protein, Glucose and GLP-1

(1) Background: There is a balance between nutrition, glycemic control, and immune response. Their roles in physiological mechanisms are essential for maintaining life quality. This study aimed to evaluate hawthorn vinegar’s metabolic effects, and describe its possible mechanism. We also pointed out several vinegar production methods to clarify the antioxidant features. (2) Methods: In the study, three vinegar techniques were applied to vinegar: traditional production of hawthorn vinegar (N), thermal pasteurization (P), and ultrasound method (U). Thirty-two female adult Wistar albino rats were randomly separated into four groups: Control, N1 (regular vinegar; 1 mL/kg bw), P1 (pasteurized vinegar; 1 mL/kg bw), and U1(ultrasound treated vinegar; 1 mL/kg bw). Vinegar was administered by oral gavage daily for 45 days. Initial and final weights, the percentage changes of body weight gains, and Gamma-Glutamyl Transferase (GGT) values of plasma and liver were measured. The total protein, globulin, and albumin values of plasma, liver, and intestinal tissue were determined. In addition, plasma glucagon-like peptide-1 (GLP-1) and glucose concentrations were evaluated. (3) Results: There was a statistical increase in total intestinal protein value and an increasing tendency in total protein in plasma and liver in group U1 compared to group Control. However, the GGT concentrations in plasma and liver were slightly lower in group U1 than in group Control. In addition, there were significant increases in plasma GLP-1 values in all experimental groups compared to the Control group (p: 0.015; 576.80 ± 56.06, 773.10 ± 28.92, 700.70 ± 17.05 and 735.00 ± 40.70; respectively groups control, N1, P1, and U1). Also, liver GLP-1 concentrations in groups P1 and U1 were higher than in group Control (p: 0.005; 968.00 ± 25.54, 1176 ± 17.54 and 1174.00 ± 44.06, respectively groups control, P1 and U1). On the other hand, significant decreases were found in plasma glucose concentrations in groups N1 and U1 as to the Control group (p: 0.02; Control: 189.90 ± 15.22, N1: 133.10 ± 7.32 and U1: 142.30 ± 4.14). Besides, liver glucose levels were lower in all experimental groups than in group Control statistically (p: 0.010; 53.47 ± 0.97, 37.99 ± 1.46, 44.52 ± 4.05 and 44.57 ± 2.39, respectively groups control, N1, P1, and U1). (4) Conclusions: The findings suggest that hawthorn vinegar can balance normal physiological conditions via intestinal health, protein profiles, and glycemic control. Additionally, ultrasound application of vinegar may improve the ability of hawthorn vinegar, and have positive effects on general health.

A New Alternative Nutritional Source Hawthorn Vinegar: How It Interacts with Protein, Glucose and GLP-1.

(1) Background: There is a balance between nutrition, glycemic control, and immune response. Their roles in physiological mechanisms are essential for maintaining life quality. This study aimed to evaluate hawthorn vinegar's metabolic effects, and describe its possible mechanism. We also pointed out several vinegar production methods to clarify the antioxidant features. (2) Methods: In the study, three vinegar techniques were applied to vinegar: traditional production of hawthorn vinegar (N), thermal pasteurization (P), and ultrasound method (U). Thirty-two female adult Wistar albino rats were randomly separated into four groups: Control, N1 (regular vinegar; 1 mL/kg bw), P1 (pasteurized vinegar; 1 mL/kg bw), and U1(ultrasound treated vinegar; 1 mL/kg bw). Vinegar was administered by oral gavage daily for 45 days. Initial and final weights, the percentage changes of body weight gains, and Gamma-Glutamyl Transferase (GGT) values of plasma and liver were measured. The total protein, globulin, and albumin values of plasma, liver, and intestinal tissue were determined. In addition, plasma glucagon-like peptide-1 (GLP-1) and glucose concentrations were evaluated. (3) Results: There was a statistical increase in total intestinal protein value and an increasing tendency in total protein in plasma and liver in group U1 compared to group Control. However, the GGT concentrations in plasma and liver were slightly lower in group U1 than in group Control. In addition, there were significant increases in plasma GLP-1 values in all experimental groups compared to the Control group (p: 0.015; 576.80 ± 56.06, 773.10 ± 28.92, 700.70 ± 17.05 and 735.00 ± 40.70; respectively groups control, N1, P1, and U1). Also, liver GLP-1 concentrations in groups P1 and U1 were higher than in group Control (p: 0.005; 968.00 ± 25.54, 1176 ± 17.54 and 1174.00 ± 44.06, respectively groups control, P1 and U1). On the other hand, significant decreases were found in plasma glucose concentrations in groups N1 and U1 as to the Control group (p: 0.02; Control: 189.90 ± 15.22, N1: 133.10 ± 7.32 and U1: 142.30 ± 4.14). Besides, liver glucose levels were lower in all experimental groups than in group Control statistically (p: 0.010; 53.47 ± 0.97, 37.99 ± 1.46, 44.52 ± 4.05 and 44.57 ± 2.39, respectively groups control, N1, P1, and U1). (4) Conclusions: The findings suggest that hawthorn vinegar can balance normal physiological conditions via intestinal health, protein profiles, and glycemic control. Additionally, ultrasound application of vinegar may improve the ability of hawthorn vinegar, and have positive effects on general health.

Effect of Supplementation of Ashwagandha (Withania somnifera) Root Powder on Body Weight Gain and Egg Quality in Layers

Background: As the demand for natural and sustainable solutions in poultry production continues to rise, ashwagandha root powder presents itself as a promising avenue for improving egg quality while aligning with consumer preferences for wholesome and nutritious products. Therefore, research trial was conducted to study the effect of supplementation of ashwagandha root powder on body weight gain and egg quality in layers during a period of 10 weeks. Methodology: One hundred and twenty White Leghorn layers were randomly divided into four treatments and reared on standard managemental conditions. The Ashwagandha root powder was supplemented with the basal diet at 0.5% level (T1), 1% (T2), 1.5 % (T3) while T0 was kept as control i.e. basal diet without ashwagandha root powder. The feed and water were offered ad libitum to experimental birds. Design used: The design of the experiment was a completely randomized design. Duncans multiple range test was used to determine significant difference among means for different treatments. Results: The result noted that the body weight change was not affected by ashwagandha root powder supplementation. Egg quality parameters viz., egg shape index, shell weight, yolk weight, yolk height, albumen weight and albumen index were not influenced by the addition of ashwagandha root powder. However, a significant (p<0.05) effect was observed on yolk index. No significant (p>0.05) difference was seen in the sensory attributes of the egg. It may be suggested that inclusion of ashwagandha root powder in the diets of layer can be improve yolk index without affecting sensory attributes of eggs in layer.

Hinesol attenuates DSS-induced ulcerative colitis through the suppression of Src-mediated NF-κB and chemokine signaling pathway.

As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1β, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

Evidence-Based Severity Assessment of Animal Models for Pancreatic Cancer

Animal models are crucial to preclinical oncological research and drug development. Animal experiments must be performed in accordance with the 3R principles of replacement and reduction, if possible, and refinement where these procedures remain crucial. In addition, European Union legislations demand a continuous refinement approach, as well as pro- and retrospective severity assessment. In this study, an objective databased severity assessment was performed in murine models for pancreatic cancer induced by orthotopic, subcutaneous, or intravenous injection of Panc02 cells. Parameters such as body weight change, distress score, perianal temperature, mouse grimace scale, burrowing, nesting behavior, and the concentration of corticosterone in plasma and its metabolites in feces were monitored during tumor progression. The most important parameters were combined into a score and mapped against a reference data set by the Relative Severity Assessment procedure (RELSA) to obtain the maximum achieved severity for each animal (RELSAmax). This scoring revealed a significantly higher RELSAmax for the orthotopic model than for the subcutaneous and intravenous models. However, compared to animal models such as pancreatitis and bile duct ligation, the pancreatic cancer models are shown to be less severe. Data-based animal welfare assessment proved to be a valuable tool for comparing the severity of differently induced cancer models.

Growth differentiation factor 15 is not modified after weight loss induced by liraglutide in South Asians and Europids with type 2 diabetes mellitus.

Glucagon-like peptide-1 receptor (GLP-1R) agonists induce weight loss in patients with type 2 diabetes mellitus (T2DM), but the underlying mechanism is unclear. Recently, the mechanism by which metformin induces weight loss could be explained by an increase in growth differentiation factor 15 (GDF15), which suppresses appetite. Therefore, we aimed to investigate whether the GLP-1R agonist liraglutide modifies plasma GDF15 levels in patients with T2DM. GDF15 levels were measured in plasma samples obtained from Dutch Europids and Dutch South Asians with T2DM before and after 26weeks of treatment with daily liraglutide (n=44) or placebo (n=50) added to standard care. At baseline, circulating GDF15 levels did not differ between South Asians and Europids with T2DM. Treatment with liraglutide, compared to placebo, decreased body weight, but did not modify plasma GDF15 levels in all patients, or when data were split by ethnicity. Also, the change in plasma GDF15 levels after treatment with liraglutide did not correlate with changes in body weight or HbA1c levels. In addition, the dose of metformin used did not correlate with baseline plasma GDF15 levels. Compared to placebo, liraglutide treatment for 26weeks does not modify plasma GDF15 levels in Dutch Europid or South Asian patients with T2DM. Thus, the weight loss induced by liraglutide is likely explained by other mechanisms beyond the GDF15 pathway. HIGHLIGHTS: What is the central question of this study? Growth differentiation factor 15 (GDF15) suppresses appetite and is increased by metformin: does the GLP-1R agonist liraglutide modify plasma GDF15 levels in patients with type 2 diabetes mellitus (T2DM)? What is the main finding and its importance? Plasma GDF15 levels did not differ between South Asians and Europids with T2DM and were not modified by 26weeks of liraglutide in either ethnicity. Moreover, there was no correlation between the changes in plasma GDF15 levels and dosage of metformin administered, changes in body weight or HbA1c levels. The appetite-suppressing effect of liraglutide is likely exerted via pathways other than GDF15.

Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study

IntroductionIt is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes.MethodsWe performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes.ResultsAt 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks.ConclusionIn this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake.Trial registrationUniversity Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/).

Taste Preferences at Different Ambient Temperatures and Associated Changes in Gut Microbiota and Body Weight in Mice.

Taste, dietary choices, and gut microbiota are often analyzed as major factors of metabolic health. Populations living in cold or hot regions have different dietary habits. This study aims to investigate the potential association among ambient temperature, food taste preferences, and cecal microbiota community profiles in mice. By exposing mice to mixed diets containing sweet, sour, salty, and bitter flavors at low (4 °C) and high (37 °C) ambient temperatures, the taste preferences of mice at both ambient temperatures were in the order of saltiness > sweetness > bitterness > sourness. Exposing mice to sweet, sour, salty, and bitter diets, respectively, revealed that in a low-temperature environment, mice consuming salty (5.00 ± 1.49 g), sweet (4.99 ± 0.35 g), and sour (3.90 ± 0.61 g) diets had significantly higher weight gain compared to those consuming normal feeds (2.34 ± 0.43 g, p < 0.05). Conversely, in a high-temperature environment, no significant changes in body weight were observed among mice consuming different flavored diets (p > 0.05). In a low-temperature environment, mice fed sour and sweet diets showed a significant difference in the gut microbiota composition when compared to those fed a normal diet. A higher abundance of Lachnospiraceae, UBA1819, and Clostridiales was identified as the most significant taxa in the sour group, and a higher abundance of Ruminiclostridium was identified in the sweet group. These differences were associated with microbial pathways involved in carbohydrate metabolism, amino acid metabolism, and energy metabolism. A high-temperature environment exhibited only minor effects on the gut microbiota profile. Overall, our findings provide evidence for temperature-modulated responses to the taste, gut microbiota functions, and body weight changes in mice.

Changes in body weight and composition, metabolic parameters, and quality of life in patients with type 2 diabetes treated with subcutaneous semaglutide in real-world clinical practice.

Subcutaneous once-weekly (ow) semaglutide is a recent treatment option for type 2 diabetes (T2D) and obesity, but real-world data on weight loss and associated changes in body composition, nutrients intake, and quality of life are still scarce. This observational, prospective clinical study involved all T2D patients starting ow semaglutide according to routine care between December 2021 and February 2022. Clinical information was collected after 6 months (T6) and 12 months (T12) from semaglutide initiation (T0). Bioelectrical Impedance Analysis (BIA) was performed to measure changes in body composition. Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the 36 - items Short Form Health Survey (SF-36) were administered as patient-reported outcomes (PROs). Changes in continuous endpoints (weight, body composition, nutrients intake, other clinical parameters, and PROs) were assessed using mixed models for repeated measurements. Overall, 90 patients (age 63.0 ± 10.0 years; diabetes duration 7.6 ± 5.9 years; 58.9% men; HbA1c 7.7 ± 1.1%; weight 95.4 ± 19.4 Kg, BMI 34.6 ± 6.4 Kg/m2; 36.7% naïve to diabetes treatment, 43.3% on metformin, 10.0% on dual oral therapy, and 10.0% treated with schemes including insulin) were included in the study. After 6 months from semaglutide initiation, body weight significantly decrease by -4.69 Kg (95%CI -6.19;-3.19) (primary endpoint). After 12 months, body weight was further reduced (-5.38 Kg; 95%CI -7.79;-2.97). At BIA, fat mass was significantly reduced by 2.1 Kg after 6 months but only slightly reduced after 12 months vs. baseline; lean mass was also significantly reduced by over 3 Kg both at 6 and 12 months. Intake of all nutrients declined in the first 6 months of therapy, although only lipids reduction reached the statistical significance (-6.73g; p=0.02). Statistically significant improvements in BMI, waist circumference, glycemic control, blood pressure and lipid profile were documented. Satisfaction with treatment (DTSQ questionnaire) and mental health (MCS score of SF-36 questionnaire) significantly increased during the follow-up. The study documented real-world benefits of semaglutide for treating obesity in T2D subjects, with important changes on clinical and patient-reported outcomes. Loss of lean mass associated with weight loss warrants attention; parallel strategies to preserve skeletal muscle and improve physical function, i.e. nutritional education and structured exercise, are of great importance.

Diluted seawater decreased weight gain and altered blood biochemical parameters in Bach Thao goats

ABSTRACT This study aimed to evaluate the effect of saline water (SW) on physiological responses, blood biochemical parameters and body weight changes in Bach Thao goats. The study was designed completely randomized with four treatments (n = 5 each), including a control as goats’ drinking fresh water (FW), goats’ drinking 0.5% SW (LSW, low SW), goats’ drinking 1.0% SW (MSW, moderate SW) and goats’ drinking 1.5% SW (HSW, high SW). The results showed that dry matter intake (DMI) decreased as SW increased (P < 0.05). Animals in the MSW group consumes highest water intake (WI), whereas animals from HSW consumed least water from 4th to 8th weeks of experiment. Respiration rate and rectal temperature in HSW were greater than those in the FW group (P < 0.05). The body weight was similar among treatments, but animals in HSW were with lower weight gain than those in the control (P < 0.05). Goats in HSW altered blood biochemical parameters in the 8th week, not for the 4th week. We concluded that Bach Thao goats drank high SW within 56 days and had negative effects on production and may effect on functions of the liver and kidney. Besides, goats from the HSW group have decreased daily WI to minimize the salt stress.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome

BackgroundSmith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. MethodsPeople with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. Results12 individuals, ages 11–39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was − 0.28 % [(95 % CI, −2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. ConclusionsIn this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

Paeoniae Decoction restores intestinal barrier dysfunction by promoting the interaction between ILC3 and gut flora

BackgroundIntestinal barrier dysfunction is a significant contributor to the recurrence and refractory of ulcerative colitis (UC). Promoting the interaction between group 3 innate lymphoid cells (ILC3s) and gut flora is a valuable strategy for mucosal repair. Paeoniae decoction (PD) is a compound commonly used in clinical treatment of UC, but its exact mechanism remains unclear. PurposeWe aimed to investigate the protective effect of PD on intestinal mucosal injury induced by dextran sulfate sodium (DSS) in chronic colitis, as well as to elucidate its potential mechanism. MethodsC57BL/6 mice were induced with chronic colitis by 2% DSS and divided into four groups: control group, model group, PD low dose (4 g/kg), and high dose (8 g/kg) group. The effectiveness of PD in treating chronic colitis mice was evaluated based on changes in body weight, colon length, colon pathological tissue scores, and the mRNA levels of inflammatory factors IL-6 and IL-1β. The expressions of intestinal epithelial tight junction proteins (ZO-1 and Occludin), IL-22, and MUC2 were observed using immunofluorescence and RT-PCR. Additionally, the proportion of ILC3 and natural cytotoxicity receptor (NCR)+ ILC3 in the colon were detected using flow cytometry. Furthermore, UHPLC-QE-MS was utilized to identify chemical components of PD and network pharmacology was employed to predict potential pathways for PD intervention in UC. Subsequently, MNK-3 cells (ILC3 in vitro cell line) and NCM460 cells were used to verify the network pharmacology results. Finally, the effects of PD on UC gut flora have been explored using in vitro fermentation and 16S rDNA techniques. ResultsThe results showed that PD significantly restored body weight and colon length in mice with chronic colitis, while also reducing colon inflammatory cell infiltration and the expression of IL-6 and IL-1β. Additionally, PD notably promoted the expression of MUC2, ZO-1, Occludin, and IL-22, as well as increasing the ratio of ILC3 and NCR+ILC3. UHPLC-QE-MS analysis identified 443 components of PD, and network pharmacology suggested that PD could target the aryl hydrocarbon receptor (AHR) signaling pathway. which was confirmed by MNK-3 cells and in vitro fermentation experiments. Furthermore, MNK-3-conditioned medium (CM) increased the expression of ZO-1 and Occludin in NCM460 cells. In addition, 16S rDNA results indicated that PD promoted the abundance of Lactobacillales, thus contributing to mucosal damage repair by activating the AHR signal in ILC3s. ConclusionIn summary, our study demonstrates that PD repairs intestinal mucosal damage in chronic colitis by regulating the interaction of gut flora with ILC3, and the specific mechanism is related to the activation of AHR signaling pathway.

Mitigating Effect of Matricin Against Benzo(a)pyrene-induced Lung Carcinogenesis in Experimental Mice Model.

Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kβ pathway.

Correlation analysis of dynamic changes of abdominal fat during rapid weight loss after bariatric surgery: A prospective magnetic resonance imaging study

ObjectiveThe factors related to the changes in the liver and abdominal adipose tissue during the rapid weight loss after bariatric surgery remain uncertain. MethodsThis study included 44 participants who had undergone sleeve gastrectomy. The study aimed to analyze changes and correlations of body weight (BW), laboratory tests, and magnetic resonance imaging (MRI) indicators of the liver and abdominal adipose tissue conducted before and after bariatric surgery at 1, 3, and 6 months. ResultsFollowing a rapid weight loss within 6 months of surgery, there was a concurrent decrease in blood glucose, blood lipids, and fat content of the liver and abdomen and the changes showed a correlation. The change of BW (ΔBW) was positively correlated with the change of hepatic proton density fat fraction (ΔPDFF) in one and three months after surgery and was positively correlated with the change of abdominal visceral fat area (ΔAVFA) in six months after surgery, (P<0.05). In one month after surgery, ΔPDFF was positively correlated with the change of aspartate aminotransferase (ΔAST), change of alanine aminotransferase (ΔALT), and change of triglyceride glucose (ΔTYG) index (P<0.05). ΔPDFF was positively correlated with the change of hepatic native T1 values (P<0.001) and was moderately negatively correlated with the change of hepatic apparent diffusion coefficient (ΔADC) values in three months after surgery (P<0.05). ConclusionΔBW can serve as an indirect indicator for evaluating changes in liver fat fraction at 1 and 3 months after bariatric surgery and indicative of changes in visceral fat 6 months after surgery. ΔPDFF was positively correlated with ΔAST, ΔALT and ΔTYG index in 1 months after surgery.