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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Catherine M. Sampson ◽  
Andrea L. Dimet ◽  
Harshini Neelakantan ◽  
Kehinde O. Ogunseye ◽  
Heather L. Stevenson ◽  
...  

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.

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 253 ◽  
Author(s):  
Yu-Sheng Chen ◽  
Hsuan-Miao Liu ◽  
Tzung-Yan Lee

Obesity has been shown to play a role in the pathogenesis of several forms of metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Ursodeoxycholic acid (UDCA) has been shown to possess antioxidant and anti-inflammatory properties and prevents mitochondrial dysfunction in the progression of obesity-associated diseases. The aim of the study was to evaluate the mechanisms of UDCA during obesity-linked hepatic mitochondrial dysfunction and obesity-associated adipose tissue macrophage-induced inflammation in obese mice. UDCA significantly decreased lipid droplets, reduced free fatty acids (FFA) and triglycerides (TG), improved mitochondrial function, and enhanced white adipose tissue browning in ob/ob mice. This is associated with increased hepatic energy expenditure, mitochondria biogenesis, and incorporation of bile acid metabolism (Abca1, Abcg1 mRNA and BSEP, FGFR4, and TGR5 protein). In addition, UDCA downregulated NF-κB and STAT3 phosphorylation by negative regulation of the expression of SOCS1 and SOCS3 signaling. These changes were accompanied by decreased angiogenesis, as shown by the downregulation of VEGF, VCAM, and TGF-βRII expression. Importantly, UDCA is equally effective in reducing whole body adiposity. This is associated with decreased adipose tissue expression of macrophage infiltration (CD11b, CD163, and CD206) and lipogenic capacity markers (lipofuscin, SREBP-1, and CD36). Furthermore, UDCA significantly upregulated adipose browning in association with upregulation of SIRT-1-PGC1-α signaling in epididymis adipose tissue (EWAT). These results suggest that multi-targeted therapies modulate glucose and lipid biosynthesis fluxes, inflammatory response, angiogenesis, and macrophage differentiation. Therefore, it may be suggested that UDCA treatment may be a novel therapeutic agent for obesity.


2015 ◽  
Vol 53 (3) ◽  
pp. 237-247
Author(s):  
C. Popescu ◽  
Violeta Bojincă ◽  
Daniela Opriş ◽  
Ruxandra Ionescu

Abstract Aim. Rheumatoid arthritis (RA) may influence not only abdominal fat, but also whole body adiposity, since it is associated with chronic inflammation and disability. The study aims to evaluate the whole body adiposity of RA patients and to assess potential influences of disease specific measures. Methods. The study was designed to include Caucasian postmenopausal female RA patients and age-matched postmenopausal female controls. Each subject underwent on the same day clinical examination, laboratory tests, whole body dual X-ray absorptiometry (DXA) composition and physical activity estimation using a self-administered questionnaire. Results. A total of 107 RA women and 104 matched controls were included. Compared to controls, the RA group had less physical activity and a higher prevalence of normal weight obesity. Overfat RA women had a significantly higher toll of inflammation, disease activity, glucocorticoid treatment and sedentary behavior. RA women with inflammation, glucocorticoid treatment and higher disease activity class had higher whole body and trunk adipose tissue indices and higher prevalence of overfat status. Glucocorticoid treatment, inflammation, disease duration and severity correlated with whole body adipose tissue and significantly predicted high adiposity content and overfat phenotypes. Conclusions. RA disease duration and severity are associated with higher whole body and regional adiposity. Low-dose glucocorticoid treatment seems to contribute to adiposity gain and redistribution. Clinicians may need to assess body composition and physical activity in RA patients in order to fully manage cardiovascular outcomes and quality of life.


2012 ◽  
Vol 32 (4) ◽  
pp. 733-741 ◽  
Author(s):  
Lílian Gonçalves Teixeira ◽  
Priscilla Ceci Lages ◽  
Tatianna Lemos Jascolka ◽  
Edenil Costa Aguilar ◽  
Fabíola Lacerda Pires Soares ◽  
...  

White tea is an unfermented tea made from young shoots of Camellia sinensis protected from sunlight to avoid polyphenol degradation. Although its levels of catechins are higher than those of green tea (derived from the same plant), there are no studies addressing the relationship between this tea and obesity associated with oxidative stress.The objective of this study was to evaluate the effect of white tea on obesity and its complications using a diet induced obesity model. Forty male C57BL/6 mice were fed a high-fat diet to induce obesity (Obese group) or the same diet supplemented with 0.5% white tea extract (Obese + WTE) for 8 weeks. Adipose tissue, serum lipid profile, and oxidative stress were studied. White tea supplementation was not able to reduce food intake, body weight, or visceral adiposity. Similarly, there were no changes in cholesterol rich lipoprotein profile between the groups. A reduction in blood triacylglycerols associated with increased cecal lipids was observed in the group fed the diet supplemented with white tea. White tea supplementation also reduced oxidative stress in liver and adipose tissue. In conclusion, white tea extract supplementation (0.5%) does not influence body weight or adiposity in obese mice. Its benefits are restricted to the reduction in oxidative stress associated with obesity and improvement of hypertriacylglycerolemia.


1996 ◽  
Vol 81 (6) ◽  
pp. 2445-2455 ◽  
Author(s):  
Robert Ross ◽  
John Rissanen ◽  
Heather Pedwell ◽  
Jennifer Clifford ◽  
Peter Shragge

Ross, Robert, John Rissanen, Heather Pedwell, Jennifer Clifford, and Peter Shragge. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 2445–2455, 1996.—The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n= 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT ( P < 0.05). The reductions in body weight (∼10%) and SAT (∼25%) and VAT volume (∼35%) were not different between groups ( P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT ( P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (∼27%) was greater ( P < 0.05) than that observed for the gluteal-femoral region (∼20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment ( P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone ( P < 0.05). Peak O2 uptake (liters) was significantly improved (∼14%) in the DA group as was muscular strength (∼20%) in the DR group ( P< 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Robin Wilson ◽  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Jay Pendse ◽  
Laura Frye ◽  
...  

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.


1994 ◽  
Vol 266 (6) ◽  
pp. E993-E1000 ◽  
Author(s):  
S. C. Blair ◽  
I. D. Caterson ◽  
G. J. Cooney

The effect of adrenalectomy (ADX) on body weight, lipogenesis, and glucose tolerance was investigated in mice made obese by a single intraperitoneal injection of gold-thioglucose (GTG). Five weeks after ADX the weight of GTG-obese mice was significantly decreased (GTG-obese+sham-ADX: 39.8 +/- 0.8 g; GTG-obese+ADX: 27.6 +/- 1.1 g; P < 0.05). ADX also reduced serum glucose (GTG-obese+sham-ADX: 16.5 +/- 0.6 mmol/l; GTG-obese+ADX: 10.8 +/- 0.5 mmol/l; P < 0.05) and serum insulin concentrations (GTG-obese+sham-ADX: 197 +/- 36 microU/ml; GTG-obese+ADX: 38 +/- 7 microU/ml; P < 0.05) of fed GTG-obese mice and greatly improved glucose tolerance. ADX lowered liver glycogen content and reduced the fatty acid content of liver, epididymal white adipose tissue (WAT), and interscapular brown adipose tissue (BAT) of fed GTG-obese mice. Lipid synthesis in liver and WAT of GTG-obese mice was decreased by ADX, but lipogenesis in BAT was increased, possibly to provide substrate for increased thermogenesis in this tissue. Effects of ADX on metabolism were not confined to GTG-injected mice, as ADX also reduced body weight and altered the glucose tolerance of age-matched control mice. ADX increased lipid synthesis in liver, WAT, and BAT of fed control mice without an increase in lipid deposition, indicating that there was increased lipid turnover in these lipogenic tissues of ADX mice. ADX reduced the fasting blood glucose concentration of both control and GTG-obese mice to a level below that of sham-ADX control mice (sham-ADX control: 6.0 +/- 0.4 mM; ADX control: 2.9 +/- 0.5 mM; ADX GTG-obese: 3.3 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Monika Młodzik-Czyżewska ◽  
Anna Malinowska ◽  
Agata Chmurzynska

AbstractA link has recently been underlined between one-carbon metabolism and body weight and body composition, suggesting that folate may account for body mass determination and lipid metabolism. The aim of this study was thus to analyze whether folate intake is associated with body weight, body mass index (BMI), body fat percentage, and liver status.409 subjects aged 20–40 were enrolled in Poznań, Poland from 2016 to 2018. Food intake was assessed using three-day food records. Folate intake was calculated based on food composition tables using the Diet 5.0 program (National Food and Nutrition Institute, Poland). Weight to 0.1 kg and height to 0.01 m were measured using an electronic scale and a stadiometer, respectively. BMI was calculated as body weight in kilograms divided by height in meters squared. Fat mass and lean body mass were determined using whole-body air-displacement plethysmography (BodPod, Cosmed, Italy). Genotyping of rs1801133 (MTHFR) was performed with TaqMan probes. The following biomarkers of liver steatosis were calculated: NAFLD liver fat score (NAFLD-LFS), fatty liver index (FLI), and hepatic steatosis index (HSI). To analyze the associations between folate intake and the measured parameters, we used multiple regression with adjustments for age, sex, and energy intake.The mean body weight was 78.57 ± 18.14 kg, BMI 25.96 ± 5.28 kg/m2, and fat percentage 29.20% ± 10.78%. The median folate intake was 299.3 μg/day. Dietary folate intake was negatively associated with body weight, BMI, and body fat percentage (p < 0.05 for all associations). Folate intake was also associated with fatty liver indices—namely HSI (p < 0.05) and FLI (p < 0.05). There was no association between folate intake and NAFLD-LFS. MTHFR rs1801133 polymorphism was not associated with any of the measured parameters.Our findings suggest that folate intake may affect body weight and composition, as well as liver status. Higher folate intake could have a protective effect against obesity, but further studies are necessary to investigate the mechanism.The authors declare that they have no conflict of interests.This work was supported by the Polish National Science Centre(grants 2014/15/B/NZ9/02134 and 2016/21/N/NZ9/01195).


2001 ◽  
Vol 137 (1) ◽  
pp. 85-96 ◽  
Author(s):  
R. SANDERSON ◽  
M. S. DHANOA ◽  
C. THOMAS ◽  
A. B. McALLAN

Growth and efficiencies of nitrogen and energy utilization for growth by 72 young British Friesian steers (initial live weight (LW) 110 kg) offered a well preserved, formic acid-treated, perennial ryegrass silage with and without supplements of fish meal were examined. Silage was offered either alone or mixed with 50, 100 or 150 g fish meal/kg silage dry matter (DM) and each diet was offered either ad libitum or intakes were restricted to 16, 19 or 22 g dietary DM/kg LW/day. Treatments were imposed over a period of 132 days. Body component weight gains were determined by comparative slaughter.Increasing the level of either feeding or fish meal increased rates of empty body weight gain linearly (P<0·001) and curvilinearly (P<0·05) respectively. Fish-meal supplementation increased rates of ash and crude protein gain (P<0·001) but, in comparison with the curvilinear response to increasing level of feeding (P<0·001), had small linear effects on fat gain (P>0·01). Consequently, in terms of whole body composition, animals given fish meal were leaner than animals offered silage alone. Fish-meal supplementation had no significant effect on the composition of the carcass but increased the concentration of protein in the liver and gastrointestinal tract.The increase in nitrogen intake associated with feeding fish meal resulted in a reduction in the efficiency of nitrogen utilization as level of fish meal increased. Nitrogen intake required for maintenance was estimated to be 1·054 g/kg LW0·75. In spite of marked differences in the composition of the empty body-weight gain, there was no evidence to support an effect of fish meal on the efficiency of metabolizable energy (ME) utilization for growth (kf) which was estimated to be 0·346 on the basis of data scaled by LW0·75. ME intake required for maintenance (MEm) was estimated to be 0·536 and 0·502 MJ/kg LW0·75 for silage alone and the 150 g fish-meal level respectively.


2015 ◽  
Vol 308 (4) ◽  
pp. E315-E323 ◽  
Author(s):  
Kana Ohyama ◽  
Yoshihito Nogusa ◽  
Katsuya Suzuki ◽  
Kosaku Shinoda ◽  
Shingo Kajimura ◽  
...  

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.


1969 ◽  
Vol 72 (1) ◽  
pp. 65-75 ◽  
Author(s):  
H. R. Gharaybeh ◽  
W. R. McManus ◽  
G. W. Arnold ◽  
M. L. Dudzinski

SUMMARYFlocks of 9-month-old Merino and Border Leicester & Merino sheep were sampled over the full range of body weights present within flocks. Six pairs of ewes and wethers of equal body weight were taken. The sheep were weighed and slaughtered after a 36 h fast. Total weights of blood, skin, head, feet, internal organs and carcasses were obtained for each animal. Each component was analysed for ash, crude protein, ether extract and total energy. Half of each carcass was dissected into bone, muscle, fat and waste.The compositions of the sheep were compared by regression analyses of weights of body components on empty body weight (EBW) between the four groups and by means of percentages of EBW. There were highly significant linear relationships between both fresh and dry weights of body components, carcass components, and chemical components with EBW; moisture content was not related to EBW. Rates of change with EBW in weights of body components, or in amounts of ash, crude protein, ether extract and energy were the same for all groups of sheep with the exceptions of bone and skin ether extract (EE) weight. However, intercepts of regression lines frequently differed, indicating that body composition differed between groups at the same EBW.All groups had the same dry weight of blood, internal organs and muscle, weight of ether extract, and total energy in the whole body at the same EBW. Border Leicester × Merinos had lighter skins with less wool, but their carcass weights were higher than Merinos. There were other differences between breeds in the chemical composition of individual components. Wethers had heavier head + feet weights and carcass bone than had ewes. There were also some sex differences in chemical composition of body components. In general, there were fewer sex than breed differences in body composition. The breed differences cannot be explained on the basis of early and later maturing types.


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