There is sex difference of obesity and it might be related with sex hormones. For instance, estrogen regulates adipose tissue function and fat deposition by activation of the sympathetic nervous system, which leads to more adiposity in subcutaneous fat instead of visceral fat. There are strong evidences for the association between obesity and cancer, predominantly cancers of digestive organs including cardia gastric cancer (GC) and cancers of hormone sensitive organs in females. The main pathways linking obesity and cancer are hyperinsulinemia/insulin resistance and abnormalities of the insulin-like growth factor (IGF)-I system, sex hormone biosynthesis and pathway, and subclinical chronic low-grade inflammation and oxidative stress. There have been several reports regarding the effect of obesity on the development of cardia GC, especially in males. The body mass index (BMI) changes from underweight or normal to overweight (23.0-24.9 kg/m²) decrease the development of non-cardia GC in males but not in females. The prognosis of GC is the better as the BMI is higher, especially in males. Estrogen can explain for the sex difference of non-cardia cancer (mainly intestinal type) regarding obesity. The peripheral adipose tissue is responsible for the process of steroid aromatization to produce sex hormones including estrogen which can explain why the obese males have better survival or less development of non-cardia GC. In terms of cardia GC, the main cause is related with frequent gastroesophageal reflux in obese males. In addition, metabolic factors such as cholesterol, glucose and IGFs are related with GC similar to other obesity related cancers.

Lisdexamfetamine dimesylate (LDX) is a psychostimulant, that has been widely recommended in recent years for the treatment of Attention-Deficit/Hyperactivity Disorder. The present study aims to evaluate the effects of LDX administration on the hepatic morphophysiology of pubertal Wistar rats, since the liver plays a central role in systemic metabolism. Male Wistar rats were randomly distributed into two experimental groups: LDX group (LDX) - received 11.3 mg/kg/day of LDX diluted in tap water; and the Control group (C) - received tap water only. Animals were treated by gavage during puberty, from postnatal day (PND) 25 to PND 65. The results showed that administration of LDX decreased white adipose tissue weight without altering overall body weight gain. Plasma biochemical analysis demonstrated an increase in plasma total cholesterol and in the concentration of hepatic transaminases in LDX rats. In addition, LDX animals exhibited an increase in N-acetyl-β-D-glucosaminidase activity, indirectly indicating macrophage recruitment to the liver. This study shows that daily exposure to LDX during puberty causes early liver inflammation and damage due, in part, to increased hepatic transaminases and associated with indirect signs of macrophage recruitment. This finding highlights the importance of monitoring the indiscriminate use of amphetamines and alerting patients to possible liver disorders.

Date fruits (Phoenix dactilyfera L.) are widely produced with huge wasted by-products (seeds/pits and fibers) in remarkable nutritional and economic potential value. This study aims to examine the impact of the functional properties of date seeds on health status and gut microbiota (GM) modulation in diabetic rats. Collected samples were dried and used in powdered form (DSP) for chemical compositions. Diabetic rats were then fed with this (5%, 10%, and 15%) versus control healthy group. Blood samples were used for glucose (BG) with lipid profiles (cholesterol; CHO), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, kidney (Urea, Criatinine) and histological function and GM were measured. Data indicated that DSP contain crude fiber, total sugar, and crude fat about 77%, 6%, and 6% respectively. Additionally, potassium was the highest while phosphorus shows the lowest (31.53 ± 1.19 vs. 2.48 ± 0.31 g/100 g DSP). Iron, calcium, sodium, and magnesium were 14.29 ± 0.59, 12.53 ± 0.49, 9.23 ± 0.22, and 7.60 ± 0.42 g/100 g DSP respectively. The 10% and 15% DSP supplementations affected the GM; Clostridium histolyticum reductions versus Bifidobacteria, Lactobacillus enhancement. Also, kidney functions and lipid profile improved especially at 15% supplementations (CHO and TG decrease vs. HDL-c increase). Valorization of date seed by-products indicates their potential health effects on lipids and kidney functions among diabetic models influenced by their antioxidant, mineral and fiber levels in association to GM composition. However, further studies are needed on humans with sustainable utilization manner of food waste.

Elevated LDL-cholesterol concentration is a major risk factor for CVD. Regular consumption of marine fish and seafood is associated with a reduced risk of CVD, although the n-3 PUFAs EPA and DHA have no cholesterol-lowering effect when given in physiologically relevant doses. Recent studies have demonstrated a lower LDL-cholesterol concentration in rodents after intake of cetoleic acid (CA, C22:1n-11), found in pelagic fish species such as herring. The primary aim was to investigate the effect of consuming capsules containing CA on LDL-cholesterol concentration in adults with overweight or obesity. The study was designed as a randomised clinical trial with two arms. Eighty participants were enrolled, and data from 75 participants were included in the statistical analyses. Participants consumed capsules containing either a CA concentrate (CECO group; 1480 mg CA and 232 mg EPA per day) or soyabean oil mixed with a n-3 PUFA concentrate without CA as comparator arm (SOYO3 group; 258 mg EPA/day) for eight weeks. The within-group changes in LDL-cholesterol were compared using ANCOVA with changes in body fat percentage as covariate. The LDL-cholesterol concentration was decreased from baseline to 8 weeks in the CECO group (n 37, median -0.1 (quartiles -0.1, 0.0) mmol/L) in comparison to the SOYO3 group (n 38, median 0.2 (quartiles 0.1, 0.2) mmol/L), with F=19.35, P=0.033 and ηp[2] = 0.212, corresponding to approximately 7% reduction in the CECO group relative to the SOYO3 group. To conclude, 8 weeks of dietary supplementation with CECO decreased the LDL-cholesterol concentration in adults with overweight or obesity.

Objective: To investigate the impact of different low density lipoprotein-cholesterol (LDL-C) levels on the risk of gastrointestinal cancer. Methods: A prospective cohort study was used to observe 126 050 in service and retired employees of Kailuan Group who participated in the physical examination for the first time in 2006 or 2008. A total of 122 734 people were finally included in the statistical analysis. The subjects were divided into five groups according to the baseline quintile of low-density lipoprotein cholesterol, namely Q1 group, Q2 group, Q3 group, Q4 group and Q5 group. The impact of different LDL-C groups on the incidence of gastrointestinal tumors was analyzed by Cox proportional hazard model. Results: During follow-up of (12.83±2.43) years, 1 460 cases of gastrointestinal tumors occurred, including 225 cases of esophageal cancer, 431 cases of gastric cancer and 804 cases of colorectal cancer. Cox proportional hazard model analysis found that after adjusting for age, sex, body mass index, high-sensitivity C-reactive protein, education, smoking, alcohol consumption, diabetes, hypertension, physical exercise, excessive salt intake, family history of cancer and taking lipid-lowering drugs, compared with Q5 group, the hazard ratio (HR) values of gastrointestinal tumors in Q1, Q2, Q3 and Q4 groups were 1.28 (95% CI: 1.08, 1.50), 1.07 (95% CI: 0.90, 1.26), 1.31 (95% CI: 1.11, 1.54) and 1.12 (95% CI: 0.94, 1.33), respectively. The HR values of esophageal cancer were 1.21 (95% CI: 0.80, 1.82), 0.82 (95% CI: 0.52, 1.30), 1.47 (95% CI: 1.00, 2.17) and 0.84 (95% CI: 0.54, 1.31), respectively. The HR values of gastric cancer were 1.05 (95% CI: 0.78, 1.41), 0.84 (95% CI: 0.61, 1.16), 1.21 (95% CI: 0.91, 1.63) and 1.04 (95% CI: 0.77, 1.41), respectively. The HR values of colorectal cancer were 1.44 (95% CI: 1.15, 1.80), 1.28 (95% CI: 1.02, 1.62), 1.31 (95% CI: 1.04, 1.65) and 1.26 (95% CI: 1.00, 1.59), respectively. Conclusions: The decrease of baseline LDL-C level may be a risk factor for gastrointestinal malignant tumors, but low LDL-C increases the risk of malignant tumors in a location dependent manner. Although low LDL-C level increases the risk of colorectal cancer, it has no significant correlation with esophageal cancer and gastric cancer.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disorder with limited treatment and manifests as hepatic lipid accumulation. The reduction of nuclear receptor corepressor 1 (NCoR1) activates the nuclear receptor PPARα, which plays a crucial role in alleviating lipid accumulation. We found that Scutellarin (Scu) regulated autophagy-mediated NCoR1/PPARα to enhance fatty acid (FA) β-oxidation and peroxisome production, thereby alleviating the lipid accumulation of MASLD. We used palmitic acid (PA)-treated human hepatocellular carcinoma (HepG2) and alpha mouse liver 12 (AML12) cells, as well as high-fat diet-fed C57BL/6J mice to evaluate the protective effect of Scu on MASLD. Scu reduced the levels of total cholesterol, triglycerides, and lipid droplets, whereas it dose-dependently increased the levels of β-hydroxybutyrate. In addition, Scu increased mRNA and protein expression of PPARα and promoted the transcriptional activity of FA β-oxidation-related target genes. In vitro, inhibition of PPARα with small interfering RNA (siRNA) abolished the activation of FA β-oxidation by Scu. Cellular thermal shift assay and drug affinity responsive target stability demonstrated that Scu did not interact directly with PPARα. Moreover, Scu increased the protein expression of 70-kDa peroxisomal membrane protein and the mRNA expression of peroxisome biogenesis-related genes. These effects were reversed by PPARα-siRNA. Scu improved the impaired autophagy while reducing the mRNA and protein expression of NCoR1. Notably, Scu reduced the colocalization of NCoR1 with PPARα and increased its colocalization with the autophagosome GABARAP. 3-MA, an autophagy inhibitor, attenuated Scu-mediated protective effects by FA β-oxidation and peroxisome biogenesis both in vitro and in vivo. In summary, Scu reduces lipid accumulation by improving the impaired autophagy, decreasing NCoR1 expression to activate PPARα, thereby simultaneously enhancing FA β-oxidation and peroxisome biogenesis, ultimately ameliorating hepatic steatosis.

Obesity, characterized by the persistent expansion of adipose tissue (AT), has become a major global health burden, necessitating the development of safe and effective therapeutic approaches to restore AT function. In this study, we utilize the enhanced hypoxic microenvironment of AT to develop a hypoxia-activated phototheranostic probe for obesity management. Caging Aza-BODIPY fluorophore (CBH) with a unique N-oxide group yields a hypoxic-responsive probe (CBH-O). Intraperitoneal injection of CBH-O formulated nanoparticles (CBH-O NPs) in obese mice enables targeted photoacoustic imaging of visceral AT, accompanied by the generation of CBH NPs with a high photothermal conversion efficiency. Photothermal modulation of visceral AT can induce white AT browning, enhance lipolysis, and alleviate inflammation, leading to a reduction of body weight (15.6%) and AT mass (65%), a decrease of cholesterol (49.1%), triglyceride (30.3%), and insulin (75.7%) in serum, a decrease in pro-inflammatory markers (IL-6, MCP-1), and an increase of the anti-inflammatory marker (IL-10). This AT hypoxic-microenvironment-responsive therapeutic strategy provides a novel and practical approach for managing obesity and its associated metabolic complications.

High-fat diets (HFDs) are a key contributor to obesity and promote oxidative stress and inflammation, which are associated with muscle atrophy and insulin resistance (IR). Passiflora edulis exhibits anti-obesity, antioxidant, and anti-inflammatory effects. The study aimed to investigate the potential benefit of P. edulis f. flavicarpa (PF) extract in preventing obesity-associated muscle atrophy and IR. The PF extract effectively inhibited cholesterol micelle solubility with an IC50 of 3431 µg/mL and decreased fat accumulation in 3T3-L1 adipocytes. Furthermore, this study investigated a model of HFD-induced IR and muscle atrophy in rats. Thirty-five male Sprague-Dawley (SD) rats were induced with obesity by HFD and were administered 250 and 500 mg/kg/day of PF extract. Rats fed with an HFD were associated with fat accumulation and oxidative stress, which promoted inflammation, muscle damage, muscle atrophy, and IR in obese rats. However, administration of PF extract effectively mitigated these effects. The PF extract decreased fat accumulation in white adipose tissues and gastrocnemius (GAS) muscle by inhibiting fat absorption and synthesis, particularly Cd36 and Hmgcr. The PF extract also notably reduced oxidative stress-induced muscle inflammation and damage via elevating nuclear factor erythroid 2-related factor 2 (Nrf2) and reducing nuclear factor kappa B (NF-κB) expressions. Additionally, PF extract was found to mechanistically prevent muscle atrophy by inhibiting Fbxo32, Trim63, and B-cell lymphoma 2 (BCL2)-associated X (Bax) expressions, while enhancing Bcl2 expression. We also found that PF extract mitigated muscle IR by upregulation of the insulin receptor substrate-1/phosphatidylinositol-3 kinase/protein kinase B (IRS-1/PI3K/AKT) pathway and Slc2a4 expression. The findings indicate that PF extract can prevent skeletal muscle loss and IR in obesity by modulating oxidative stress, inflammation, and activating IRS-1/PI3K/AKT signaling pathway.