The ascending prevalence of obesity in recent decades is commonly associated with soaring morbidity and mortality rates, resulting in increased health-care costs and decreased quality of life. A systemic state of stress characterized by low-grade inflammation and pathological formation of reactive oxygen species (ROS) usually manifests in obesity. The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) is the master regulator of the redox homeostasis and plays a critical role in the resolution of inflammation. Here, we show that the natural isothiocyanate and potent NRF2 activator sulforaphane reverses diet-induced obesity through a predominantly, but not exclusively, NRF2-dependent mechanism that requires a functional leptin receptor signaling and hyperleptinemia. Sulforaphane does not reduce the body weight or food intake of lean mice but induces an anorectic response when coadministered with exogenous leptin. Leptin-deficient Lepob/ob mice and leptin receptor mutant Leprdb/db mice display resistance to the weight-reducing effect of sulforaphane, supporting the conclusion that the antiobesity effect of sulforaphane requires functional leptin receptor signaling. Furthermore, our results suggest the skeletal muscle as the most notable site of action of sulforaphane whose peripheral NRF2 action signals to alleviate leptin resistance. Transcriptional profiling of six major metabolically relevant tissues highlights that sulforaphane suppresses fatty acid synthesis while promoting ribosome biogenesis, reducing ROS accumulation, and resolving inflammation, therefore representing a unique transcriptional program that leads to protection from obesity. Our findings argue for clinical evaluation of sulforaphane for weight loss and obesity-associated metabolic disorders.

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Diabetes self-management (DSM) practices are an important determinant of health-related outcomes, including health-related quality of life (HRQOL). The purpose of this study is to explore DSM practices and their relationship with the HRQOL of patients with type 2 diabetes in primary health care centers (PHCCs) in Qatar. In this cross-sectional study, data were collected from PHCC patients with diabetes via interview-administered questionnaires by utilizing two instruments: the DSM questionnaire (DSMQ) and the HRQOL Short Form (SF-12). Frequencies were calculated for categorical variables and medians were calculated for continuous variables that were not normally distributed. A statistical comparison between groups was conducted using chi-square for categorical data. Binary logistic regression was utilized to examine the relationship between the significant independent factors and the dependent variables. A total of 105 patients completed the questionnaire, 51.4% of whom were male. Approximately half of the participants (48.6%) reported poor overall DSM practices, and 50.5% reported poor physical health quality of life (PC) and mental health quality of life (MC). Female participants showed significantly higher odds of reporting poor DSM than male participants (OR, 4.77; 95% CI, 1.92–11.86; p = 0.001). Participants with a secondary education (OR, 0.18; 95% CI, 0.04–0.81; p = 0.025) and university education (OR, 0.18; 95% CI, 0.04–0.84; p = 0.029) showed significantly lower odds of reporting poor DSM than participants with no/primary education. Older participants showed higher odds of reporting poor PC than younger participants (OR 11.04, 95% CI, 1.47–82.76 and OR 8.32; 95% CI, 1.10–62.86, respectively). Females also had higher odds for poor PC than males (OR 7.08; 95% CI, 2.21–22.67), while participants with a secondary (OR, 0.13; 95% CI, 0.03–0.62; p = 0.010) and university education (OR, 0.11; 95% CI, 0.02–0.57; p = 0.008) showed significantly lower odds of reporting poor MC. In conclusion, patients with diabetes reported poor overall DSM practices and poor HRQOL. Our findings suggest intensifying efforts to deliver culturally appropriate DSM education to patients and to empower patients to take charge of their health.

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Background: Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O2 tension are not well known. Consequently, this study aimed to evaluate the impact of DHA on markers of inflammation, metabolism, apoptosis, and oxidative stress in 3T3-L1 cell adipocytes exposed to low O2 tension (1% O2) induced hypoxia. Methods: The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated. Results: DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY). Conclusion: This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis.

Background: Aspartame is a widely employed synthetic sweetener used in diet control and by diabetic patients. Its safety based on the findings of the previous studies showed controversy. Aim of the Work: The aim of this study was to demonstrate the chronic effect of aspartame on the structure of the kidney in the newborn, adult and old albino rats. Materials and Methods: In this work, 60 albino rats were used, 40 of which were three month old, while the remaining 20 rats were twelve month old at the beginning of the study. They were divided into 3 groups: A, B, C and every group was subdivided into 2 subgroups; control and treated. Group A included 20 female albino rats aged three months. The treated subgroup A received aspartame in a dose of 20 mg/kg/day dissolved in tap water through an intragastric tube for three months pregestational and during the gestational period. The offspring numbers, body and kidney weights were estimated and statistically analyzed and their kidneys were examined histopathologically. Group B included 20 adult albino rats aged three months. Group C included 20 albino rats aged twelve months. The treated animals of groups B and C were given aspartame in the same dose and by the same route as in group A for six months. The kidney specimens from all groups were processed for light microscopic examination using Haematoxylin and Eosin stain. Toluidine blue stain was used for the semithin sections of the adult rat's kidney specimens. Electron microscopic study of the proximal convoluted tubules of the adult kidney was done. Results: The results of this study revealed a delayed development of the kidney of the newborn rat with the maternal aspartame administration in addition to degenerative changes in the renal corpuscles and tubules. The statistical analysis of the newborns' body and kidney weights showed significant reduction. The kidneys of aspartame-treated adult rats showed degenerative changes affecting the renal corpuscles and tubules. The renal corpuscles had shrunken glomerular capillary tuft and widened Bowman`s space. Some of which revealed irregularity of Bowman`s capsule. The renal tubules showed dilatation of the tubular lumen, dense nuclei and vacuolated cytoplasm with sloughed epithelial lining cells. Congested and dilated blood vessels were also observed. The ultrastructural study of the proximal convoluted tubular lining cells revealed an extensive damage of the cytoplasmic organelles and the brush border. Aspartame-treated aged rat's kidney showed massive degenerative changes in comparison to the other treated groups. All the renal tubules showed thinning of their lining epithelium with dilated lumen. Some of which had destructed or thickened basement membrane. Others showed accumulation of dense acidophilic casts inside the lumen. Dilated and congested blood vessels with vacuolated cytoplasm were noticed. Conclusion: It was concluded from this study that aspartame had nephrotoxic effects on the newborn, adult and aged rats.

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Background Oxidative stress plays an important role in pathogenesis of obesity. Heme oxygenase1 (HMOX1) is a rate‐limiting enzyme functioning in heme catabolism, which modulates oxidative stress. Sulforaphane (SFN), a bioactive compound, and previous studies suggest that SFN could be a potential anti‐obesity drug. The current study investigates HOMX1 gene expression changes in skeletal muscles (SkM) of wild type diet‐induced obesity (DIO). Methods Age and weight matched of wild‐type CD1 and the knockout of nuclear factor (erythroid‐derived 2)‐like 2 (NrF2) mice were fed a high fat diet for 16 weeks to induce DIO. Then, each group was further divided in to two subgroups and received daily intraperitoneal (ip) injections of either vehicle (25 μl) or SFN (5 mg/kg BW) for four weeks. Body weights was monitored daily during treatment. Skeletal muscle samples were assessed for HMOX1 mRNA expression using RT‐PCR. Results The body weights of SFN treated WT mice have decreased significantly by ‐15.1%, p 0.004, while it decreased insignificantly by ‐2.5% in KO NrF2‐/‐, p=0.512. HMOX1 expression in (SkM) of WT mice was significantly upregulated following SFN treatment by seven folds, P‐value of 0.024, but insignificantly increased by 1.2 folds in (SkM) of KO NrF2‐/‐ mice, p=0.176. Conclusion SFN induces upregulation of heme oxygenase expression in wild‐type mice's skeletal muscle but not the KO Nrf2 mice. The upregulation of HOMX1 in skeletal muscle could refer to the role of the Nrf2 pathway in muscle tissue as the main target for SFN treatment in obesity.