Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice

Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites’ abundances. Collectively, these results provide a novel foundation for future investigations.

Levels of dopamine, 5-hydroxytryptamine and their metabolites in the striatum of rats of various strains receiving a high-calorie diet

The aim of this work was to study the effect of a high fat and carbohydrate diet (HFCD) and quercetin supplementation on the levels of dopamine (DA), serotonin (5-HT) and their metabolites in Wistar, DA transporter knockout (DAT-KO) and obese Zucker fa/fa rats. Animals received a control diet or HFCD for 62 days. Wistar and Zucker fa/fa rats received quercetin. The contents of DA, 5-HT, norepinephrine (NE), dioxyphenyl acetate (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolyl acetate (5-HIIA) in the striatum were determined by high-performance liquid chromatography (HPLC). DAT-KO homozygotes had lowered DA and increased HVA and DOPAC compared to Wistar rats. HFCD did not affect the content of NE and 5-HT. 5-HT was increased in DAT-KO homozygotes compared with Wistar receiving a control diet. 5-HIIA accumulated in larger amounts in DAT-KO compared to Wistar with the exception of those receiving quercetin with a control diet. Quercetin did not affect the levels of DA, 5-HT and their metabolites.

Deletion of PTP 1B from Brain Neurons Partly Protects Mice from Diet-Induced Obesity and Minimally Improves Fertility

Reproductive dysfunction in women has been linked to high calorie diet (HCD)-feeding and obesity. Central resistance to leptin and insulin have been shown to accompany diet-induced infertility in rodent studies, and we have previously shown that deleting suppressor of cytokine signaling 3, which is a negative regulator of leptin signaling, from all forebrain neurons partially protects mice from HCD-induced infertility. In this study, we were interested in exploring the role of protein tyrosine phosphatase 1B (PTP1B), which is a negative regulator of both leptin and insulin signaling, in the pathophysiology of HCD-induced obesity and infertility. To this end, we generated male and female neuron-specific PTP1B knockout mice and compared their body weight gain, food intake, glucose tolerance and fertility to control littermates under both normal calorie diet-feeding and HCD-feeding conditions. Both male and female mice with neuronal PTP1B deletion exhibited slower body weight gain in response to HCD-feeding, yet only male knockout mice exhibited improved glucose tolerance compared with controls. Neuronal PTP1B deletion improved the time to first litter in HCD-fed mice, but did not protect female mice from eventual HCD-induced infertility. While the mice fed a normal caloric diet remained fertile throughout the 150 day period of assessment, HCD-fed females became infertile after producing only a single litter, regardless of their genotype. These data show that neuronal PTP1B deletion is able to partially protect mice from HCD-induced obesity, but is not a critical mediator of HCD-induced infertility.

Artichoke and Bergamot Phytosome Alliance: A Randomized Double Blind Clinical Trial in Mild Hypercholesterolemia

Botanicals are natural alternatives to pharmacological therapies that aim at reducing hypercholesterolemia. In this context, despite bergamot being effective in modulating lipid profile, some subjects failed to achieve a satisfactory response to supplementation. The aim of this study was to evaluate whether the association of 600 mg of bergamot phytosome® (from Citrus Bergamia Risso) and 100 mg of artichoke leaf standardized dry extract (from Cynara cardunculus L.) can be an alternative in patients with mild hypercholesterolemia who are poor responders to bergamot in a 2-month randomized placebo-controlled trial. Sixty overweight adults were randomized into two groups: 30 were supplemented and 30 received a placebo. The metabolic parameters and DXA body composition were evaluated at the start, after 30 and 60 days. Between the two groups, total and LDL cholesterol in the supplemented group (compared to placebo) showed significant decreases overtime. A significant reduction of waist circumference and visceral adipose tissue (VAT) was recorded in the supplemented group (compared to placebo), even in subjects who did not follow a low-calorie diet. In conclusion, the synergism between Citrus Bergamia polyphenols and Cynara cardunculus extracts may be an effective option and may potentially broaden the therapeutic role of botanicals in dyslipidemic patients.

Evaluation of the effectiveness of diet therapy in the elderly with obesity and non-alcoholic fatty liver disease

The aim of the study was to evaluate the effectiveness of a standard reduced-calorie diet in elderly subjects with obesity and nonalcoholic fatty liver disease (NAFLD).Materials and Methods: 60 women with I-III degree obesity and NAFLD were examined. Metabolic status was assessed by indirect calorimetry and body composition indices using bioimpedance spectroscopy. Biochemical indices in blood serum were determined on a biochemical analyzer “KONELAB Prime 60i”. SPSS Statistics 23.0 program was used for statistical data processing.Results and Discussion: It was found that resting energy expenditure was significantly higher in middle-aged women (1896.8±46.5 kcal/d) with obesity and NAFLD than in elderly women (1691.6±34.2 kcal/d). Fat oxidation rate was significantly lower in elderly women (66.8±7 g/day) than in middle-aged women (70.8±9 g/day). The elderly patients received a variant of the standard diet with reduced caloric content for 10 days. Against the background of diet therapy, a significant decrease in glucose, total cholesterol, LDL, triglycerides, as well as fat mass, total fluid and visceral fat area was observed in elderly patients with obesity and NAFLD. However, the use of a standard reduced-calorie diet resulted in a slight elevation of serum uric acid levels and a significant decrease in muscle mass.Conclusions: the selection of specialized diets is recommended for elderly patients with obesity and NAFLD when prescribing diet therapy, which will not only prevent the decrease of muscle mass and increase of uric acid but also improve the effectiveness of treatment measures in obesity by preventing the development and progression of its complications.

Liraglutide (Saxenda)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses liraglutide 6 mg/mL (Saxenda). Indication under review : Indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial BMI of: 30 kg/m2 or greater (obesity), or 27 kg/m2 or greater (overweight) in the presence of at least 1 weight-related comorbidity (e.g., hypertension, type 2 diabetes, or dyslipidemia) and who have failed a previous weight management intervention.

Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients

Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus cytome assay—CBMN) in severely obese patients (BMI ≥ 35 kg m−2) after 3-weeks on a 567 kcal, hospital-controlled VLCD. This is the first study on the permanent genomic (in)stability in such VLCD patients. VLCDs caused significant decreases in weight (loss), parameters of the lipid profile, urea, insulin resistance, and reduced glutathione (GSH). Genomic instability parameters were lowered by half, reaching reference values usually found in the healthy population. A correlation was found between GSH decrease and reduced DNA damage. VLCDs revealed susceptible individuals with remaining higher DNA damage for further monitoring. In a highly heterogeneous group (class II and III in obesity, differences in weight, BMI, and other categories) consisting of 26 obese patients, the approach demonstrated its usefulness and benefits in health improvement, enabling an individual approach to further monitoring, diagnosis, treatment, and risk assessment based on changing anthropometric/biochemical VLCD parameters, and CBMN results.

Progression of a 2nd type diabetes mellitus model on mice with usage of a calorie diet

Type 2 diabetes accounts for up to 90% of all diabetes cases. It is known that people with type 2 diabetes are often obese. Long-term complications also include problems with the cardiovascular, nervous and urinary systems. The model of type 2 diabetes mellitus based on a diet rich of fat and carbohydrates was used in the work. We observed a significant increase in the body weight of mice and sugar levels in their blood. Morphometric analysis of the pancreas showed an increase of its mass coefficient. Tactile sensitivity measurement showed an increase in its threshold. The developed model is quite suitable for analyzing the diabetes progression and its side effects on the body. Key words: diabetes mellitus type 2, obesity, pancreas, tactile sensitivity.