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

AbstractTreatment 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.

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Sleeve Gastrectomy Decreases Body Weight, Whole-Body Adiposity, and Blood Pressure Even in Aged Diet-Induced Obese Rats

Obesity Surgery ◽

10.1007/s11695-015-1919-9 ◽

2015 ◽

Vol 26 (7) ◽

pp. 1549-1558 ◽

Cited By ~ 6

Author(s):

Rafael Moncada ◽

Amaia Rodríguez ◽

Sara Becerril ◽

Leire Méndez-Giménez ◽

Víctor Valentí ◽

...

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Sleeve Gastrectomy ◽

Whole Body ◽

Body Adiposity ◽

Obese Rats

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Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice

Scientific Reports ◽

10.1038/s41598-021-85051-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Catherine M. Sampson ◽

Andrea L. Dimet ◽

Harshini Neelakantan ◽

Kehinde O. Ogunseye ◽

Heather L. Stevenson ◽

...

Keyword(s):

Body Composition ◽

Body Weight ◽

Adipose Tissue ◽

Weight Ratio ◽

Whole Body ◽

Obese Mice ◽

Calorie Diet ◽

Diet Control ◽

Physiological Benefits ◽

Body Lean Mass

AbstractObesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.

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Evaluation of a New Preparation of Urokinase

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649107 ◽

1973 ◽

Vol 30 (01) ◽

pp. 114-122

Author(s):

C.R.M Prentice ◽

K.M Rogers ◽

G.P McNicol

Keyword(s):

Body Weight ◽

Maintenance Therapy ◽

Initial Dose ◽

Fibrinolytic Activity ◽

Pharmacological Effect ◽

Whole Body ◽

Fibrinolytic Agent ◽

Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

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The effect of pre-resection obesity on post-resection body composition after 75% small bowel resection in rats

Scientific Reports ◽

10.1038/s41598-021-92510-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Neesha S. Patel ◽

Ujwal R. Yanala ◽

Shruthishree Aravind ◽

Roger D. Reidelberger ◽

Jon S. Thompson ◽

...

Keyword(s):

Body Weight ◽

Small Bowel ◽

Lean Mass ◽

Bowel Resection ◽

Small Bowel Resection ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Massive Resection ◽

Obese Rats

AbstractIn patients with short bowel syndrome, an elevated pre-resection Body Mass Index may be protective of post-resection body composition. We hypothesized that rats with diet-induced obesity would lose less lean body mass after undergoing massive small bowel resection compared to non-obese rats. Rats (CD IGS; age = 2 mo; N = 80) were randomly assigned to either a high-fat (obese rats) or a low-fat diet (non-obese rats), and fed ad lib for six months. Each diet group then was randomized to either underwent a 75% distal small bowel resection (massive resection) or small bowel transection with re-anastomosis (sham resection). All rats then were fed ad lib with an intermediate-fat diet (25% of total calories) for two months. Body weight and quantitative magnetic resonance-determined body composition were monitored. Preoperative body weight was 884 ± 95 versus 741 ± 75 g, and preoperative percent body fat was 35.8 ± 3.9 versus 24.9 ± 4.6%; high-fat vs. low fat diet, respectively (p < 0.0001); preoperative diet type had no effect on lean mass. Regarding total body weight, massive resection produced an 18% versus 5% decrease in high-fat versus low-fat rats respectively, while sham resection produced a 2% decrease vs. a 7% increase, respectively (p < 0.0001, preoperative vs. necropsy data). Sham resection had no effect on lean mass; after massive resection, both high-fat and low-fat rats lost lean mass, but these changes were not different between the latter two rat groups. The high-fat diet and low-fat diet induced obesity and marginal obesity, respectively. The massive resection produced greater weight loss in high-fat rats compared to low-fat rats. The type of dietary preconditioning had no effect on lean mass loss after massive resection. A protective effect of pre-existing obesity on lean mass after massive intestinal resection was not demonstrated.

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Bertholletia excelsa Seeds Reduce Anxiety-Like Behavior, Lipids, and Overweight in Mice

Molecules ◽

10.3390/molecules26113212 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3212

Author(s):

Oswaldo Frausto-González ◽

Claudia J. Bautista ◽

Fernando Narváez-González ◽

Alberto Hernandez-Leon ◽

Erika Estrada-Camarena ◽

...

Keyword(s):

Body Weight ◽

Body Weight Gain ◽

Chronic Administration ◽

Testicular Tissue ◽

Lipid Lowering ◽

Bertholletia Excelsa ◽

Calorie Diet ◽

Hole Board ◽

Lipid Reduction ◽

Hypercaloric Diet

Overweight, obesity, and psychiatric disorders are serious health problems. To evidence the anxiolytic-like effects and lipid reduction in mice receiving a high-calorie diet and Bertholletia excelsa seeds in a nonpolar extract (SBHX, 30 and 300 mg/kg), animals were assessed in open-field, hole-board, and elevated plus-maze tests. SBHX (3 and 10 mg/kg) potentiated the pentobarbital-induced hypnosis. Chronic administration of SBHX for 40 days was given to mice fed with a hypercaloric diet to determine the relationship between water and food intake vs. changes in body weight. Testes, epididymal white adipose tissue (eWAT), and liver were dissected to analyze fat content, triglycerides, cholesterol, and histological effects after administering the hypercaloric diet and SBHX. Fatty acids, such as palmitoleic acid (0.14%), palmitic acid (21.42%), linoleic acid (11.02%), oleic acid (59.97%), and stearic acid (7.44%), were identified as constituents of SBHX, producing significant anxiolytic-like effects and preventing body-weight gain in mice receiving the hypercaloric diet without altering their water or food consumption. There was also a lipid-lowering effect on the testicular tissue and eWAT and a reduction of adipocyte area in eWAT. Our data evidence beneficial properties of B. excelsa seeds influencing global health concerns such as obesity and anxiety.

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In Vivo Radioprotective Activity of Cell-Permeable Bifunctional Antioxidant Enzyme GST-TAT-SOD against Whole-Body Ionizing Irradiation in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/2689051 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Jianru Pan ◽

Huocong He ◽

Ying Su ◽

Guangjin Zheng ◽

Junxin Wu ◽

...

Keyword(s):

Growth Rate ◽

Antioxidant Activity ◽

Body Weight ◽

Whole Body ◽

White Pulp ◽

Radioprotective Activity ◽

Significant Difference ◽

Wbc Count

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.

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Growth and zinc homeostasis in the severely Zn-deficient rat

British Journal Of Nutrition ◽

10.1079/bjn19840122 ◽

1984 ◽

Vol 52 (3) ◽

pp. 545-560 ◽

Cited By ~ 86

Author(s):

R. Giugliano ◽

D. J. Millward

Keyword(s):

Body Weight ◽

Growth Rates ◽

Control Diet ◽

Rate Of Change ◽

Zinc Homeostasis ◽

Whole Body ◽

Zn Deficiency ◽

Control Groups ◽

Body Weights ◽

Cyclic Changes

1. Male weanling rats were fed on diets either adequate (55 mg/kg), or severely deficient (0.4 mg/kg) in zinc, either ad lib. or in restricted amounts in four experiments. Measurements were made of growth rates and Zn contents of muscle and several individual tissues.2. Zn-deficient rats exhibited the expected symptoms of deficiency including growth retardation, cyclic changes in food intake and body-weight.3. Zn deficiency specifically reduced whole body and muscle growth rates as indicated by the fact that (a) growth rates were lower in ad lib.-fed Zn-deficient rats compared with rats pair-fed on the control diet in two experiments, (b) Zn supplementation increased body-weights of Zn-deficient rats given a restricted amount of diet at a level at which they maintained weight if unsupplemented, (c) Zn supplementation maintained body-weights of Zn-deficient rats fed a restricted amount of diet at a level at which they lost weight if unsupplemented (d) since the ratio, muscle mass:body-weight was lower in the Zn-deficient rats than in the pair-fed control groups, the reduction in muscle mass was greater than the reduction in body-weight.4. Zn concentrations were maintained in muscle, spleen and thymus, reduced in comparison to some but not all control groups in liver, kidney, testis and intestine, and markedly reduced in plasma and bone. In plasma, Zn concentrations varied inversely with the rate of change of body-weight during the cyclic changes in body-weight.5. Calculation of the total Zn in the tissues examined showed a marked increase in muscle Zn with a similar loss from bone, indicating that Zn can be redistributed from bone to allow the growth of other tissues.6. The magnitude of the increase in muscle Zn in the severely Zn-deficient rat, together with the magnitude of the total losses of muscle tissue during the catabolic phases of the cycling, indicate that in the Zn-deficient rat Zn may be highly conserved in catabolic states.

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Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00410.2020 ◽

2021 ◽

Author(s):

Tai-Yu Huang ◽

Melissa A. Linden ◽

Scott E. Fuller ◽

Felicia R Goldsmith ◽

Jacob Simon ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Exercise Training ◽

Fat Mass ◽

Mitochondrial Fission ◽

Critical Role ◽

Oxidative Capacity ◽

Low Fat Diet ◽

Ketogenic Diets ◽

Diet And Exercise

Ketogenic diets (KD) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). A high fat, carbohydrate-deficient NPKD (16.1% protein, 83.9% fat, 0% carbohydrate) was given to C57BL/6J male mice for 6 weeks, while controls received a low fat diet with similar protein (15.9% protein, 11.9% fat, 72.2% carbohydrate). On week four of the diet, mice began treadmill training 5 days/week, 60 min/day for 3 weeks. NPKD-fed mice increased body weight and fat mass, while ExTr negated a continued rise in adiposity. ExTr increased intramuscular glycogen, while the NPKD increased intramuscular triglycerides. Neither the NPKD nor ExTr alone altered mitochondrial content; however, in combination, the NPKD-ExTr group showed increases in PGC-1α, as well as markers of mitochondrial fission and fusion. Pyruvate oxidative capacity was unchanged by either intervention, while ExTr increased leucine oxidation in NPKD-fed mice. Lipid metabolism pathways had the most notable changes as the NPKD and ExTr interventions both enhanced mitochondrial and peroxisomal lipid oxidation and many adaptations were additive or synergistic. Overall these results suggest a combination of a NPKD and ExTr induces additive and/or synergistic adaptations in skeletal muscle oxidative capacity.

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Analysis of Red Cell Mass and Plasma Volume in Patients With Polycythemia

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-89-aorcma ◽

2005 ◽

Vol 129 (1) ◽

pp. 89-91 ◽

Cited By ~ 2

Author(s):

Mordechai Lorberboym ◽

Naomi Rahimi-Levene ◽

Helena Lipszyc ◽

Chun K. Kim

Keyword(s):

Body Weight ◽

Plasma Volume ◽

Cell Mass ◽

Mean Value ◽

Whole Body ◽

Red Cell ◽

Volume Data ◽

Red Cell Mass ◽

The Mean ◽

Iodine 125

Abstract Context.—Polycythemia describes an increased proportion of red blood cells in the peripheral blood. In absolute polycythemia, there is increased red cell mass (RCM) with normal plasma volume, in contrast with apparent polycythemia, in which there is increased or normal RCM and decreased plasma volume. In order to deliver the appropriate treatment it is necessary to differentiate between the two. Objective.—A retrospective analysis of RCM and plasma volume data are presented, with special attention to different methods of RCM interpretation. Design.—The measurements of RCM and plasma volume in 64 patients were compared with the venous and whole-body packed cell volume, and the incidence of absolute and apparent polycythemia was determined for increasing hematocrit levels. Measurements of RCM and plasma volume were performed using chromium 51–labeled red cells and iodine 125–labeled albumin, respectively. The measured RCM of each patient was expressed as a percentage of the mean expected RCM and was also defined as being within or outside the range of 2 SD of the mean. The results were also expressed in the traditional manner of mL/kg body weight. Results.—Twenty-one patients (13 women and 8 men) had absolute polycythemia. None of them had an increased plasma volume beyond 2 SD of the mean. When expressed according to the criteria of mL/kg body weight, 17 of the 21 patients had abnormally increased RCM, but 4 patients (19%) had a normal RCM value. Twenty-eight patients had apparent polycythemia. The remaining 15 patients had normal RCM and plasma volume. Conclusions.—The measurement of RCM and plasma volume is a simple and necessary procedure in the evaluation of polycythemia. In obese patients, the expression of RCM in mL/kg body weight lacks precision, considering that adipose tissue is hypovascular. The results of RCM are best described as being within or beyond 2 SD of the mean value.

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Influence of gender on OVA-induced airway inflammation in C57/B6J mice on a high-fat diet

European Journal of Inflammation ◽

10.1177/2058739218760946 ◽

2018 ◽

Vol 16 ◽

pp. 205873921876094 ◽

Cited By ~ 1

Author(s):

Gang Yu ◽

Lili Zhu ◽

Haiyan Li ◽

Youyou Shao ◽

Lei Chong ◽

...

Keyword(s):

Body Weight ◽

High Fat Diet ◽

Inflammatory Cells ◽

Normal Weight ◽

Male Mice ◽

High Fat ◽

Low Fat ◽

Control Male ◽

Low Fat Diet ◽

Asthma Group

Overweight/obesity has been suggested as a risk factor for asthma development, and prospective studies have confirmed that high body weight precedes asthma symptoms. However, the nature of the association between overweight/obese status and asthma remains unclear. Animal models of obesity-related asthma are very useful for understanding disease pathophysiology. Although C57/B6J mice are the most widely used animal model for researching obesity-related asthma, gender differences are not always taken into consideration. Therefore, to explore the effect of gender on the development of obesity-related asthma, both female and male C57/B6J mice were used in this study. The mice were fed with a high-fat diet or a low-fat diet as control. Body weight, body length, liver weight, and Lee’s Index were used to evaluate obesity status, and lung histology, lung inflammatory cells infiltration, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined for asthma evaluation. We found that the mean body weight of male mice on a high-fat diet gradually increased and was significantly higher than control male mice on a low-fat diet ( P < 0.01), while no significant differences were found between female mice at the end of 12 weeks of feeding. Furthermore, the obese asthma group female and male mice exhibited significantly high inflammatory cells infiltration than normal weight or obese female and male mice ( P < 0.01). However, the obese asthma group presented higher Neu infiltration, Th1 cytokine, and interferon gamma (IFNγ) concentrations in BALF than the asthma group in both the genders ( P < 0.01). In conclusion, both female and male mice are suitable for the obesity-related asthma model, although male mice might be more stable. Besides, obesity-related asthma is not Th2 type asthma.

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