scholarly journals α-Methyl-L-Tryptophan as a Weight-Loss Agent in Multiple Models of Obesity in Mice

2021 ◽  
Author(s):  
Sathish Sivaprakasam ◽  
Sabarish Ramachandran ◽  
Mohd Omar Faruk Sikder ◽  
Yangzom Doma Bhutia ◽  
Mitchell Wachtel ◽  
...  

a-Methyl-L-tryptophan (a-MLT) is currently in use as a tracer in its 11C-labeled form to monitor the health of serotonergic neurons in humans. In the present study, we found this compound to function as an effective weight-loss agent at pharmacological doses in multiple models of obesity in mice. The drug was able to reduce the body weight when given orally in drinking water (1 mg/ml) in three different models of obesity: normal mice on high-fat diet, Slc6a14-null mice on high-fat diet, and ob/ob mice on normal diet. Only the L-enantiomer (a-MLT) was active while the D-enantiomer (a-MDT) had negligible activity. The weight-loss effect was freely reversible, with the weight gain resuming soon after the withdrawal of the drug. All three models of obesity were associated with hyperglycemia, insulin resistance, and hepatic steatosis; a-MLT reversed these features. There was a decrease in food intake in the treatment group. Mice on a high-fat diet showed decreased cholesterol and protein in the serum when treated with a-MLT; there was however no evidence of liver and kidney dysfunction. Plasma amino acid profile indicated a significant decrease in the levels of specific amino acids, including tryptophan; but the levels of arginine were increased. We conclude that a-MLT is an effective, reversible, and orally active drug for the treatment of obesity and metabolic syndrome.

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 484
Author(s):  
Rόisín C. Thomas ◽  
Ramiar Kheder ◽  
Hasanain Alaridhee ◽  
Naomi Martin ◽  
Cordula M. Stover

Background and objectives: Overnutrition leads to a metabolic and inflammatory response that includes the activation of Complement. Properdin is the only amplifier of complement activation and increases the provision of complement activation products. Its absence has previously been shown to lead to increased obesity in mice on a high fat diet. The aim of this study was to determine ways in which properdin contributes to a less pronounced obese phenotype. Materials and Methods: Wild type (WT) and properdin deficient mice (KO) were fed a high-fat diet (HFD) for up to 12 weeks. Results: There was a significant increase in liver triglyceride content in the KO HFD group compared to WT on HFD. WT developed steatosis. KO had an additional inflammatory component (steatohepatitis). Analysis of AKT signalling by phosphorylation array supported a decrease in insulin sensitivity which was greater for KO than WT in liver and kidney. There was a significant decrease of C5L2 in the fat membranes of the KO HFD group compared to the WT HFD group. Circulating microparticles in KO HFD group showed lower presence of C5L2. Expression of the fatty acid transporter CD36 in adipose tissue was increased in KO on HFD and was also significantly increased in plasma of KO HFD mice compared to WT on HFD. CD36 was elevated on microparticles from KO on HFD. Ultrastructural changes consistent with obesity-associated glomerulopathy were observed for both HFD fed genotypes, but tubular strain was greater in KO. Conclusion: Our work demonstrates that complement properdin is a dominant factor in limiting the severity of obesity-associated conditions that impact on liver and kidney. The two receptors, C5L2 and CD36, are downstream of the activity exerted by properdin.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3576
Author(s):  
Su Bin Hwang ◽  
Bog-Hieu Lee

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (−39.1%) and fat weight (−26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (−20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder’s functional and health-promoting benefits associated with anti-obesity and antidiabetes.


2003 ◽  
Vol 31 (02) ◽  
pp. 213-223
Author(s):  
H. G. Choi ◽  
D. H. Kwak ◽  
J. Y. Kim ◽  
Y. J. Choi ◽  
B. S. Kil ◽  
...  

It has been generally accepted that Hwangryunjihwang-tang (H-tang) is a useful prescription for treating polydipsia and to prevent obesity induced by a high-fat diet. The aim of this study was to clarify whether H-tang improved reproductive dysfunction caused by obesity in mice. Mice were fed a high density protein and lipid diet for 4 weeks, followed by administration of H-tang at 480 mg/kg body weight per day for 4 days. Thereafter, changes of body weight, ovulation rate, in vitro and in vivo fertilization, embryonic development and implantation rate were measured. H-tang markedly reduced the body weight of obese mice fed a high-fat diet, but not mice fed a normal diet. H-tang significantly improved ovulation rates, in vitro and in vivo fertilization rates and embryonic development. These results indicate pharmacological reversal of reproductive dysfunction caused by obesity, perhaps by adjusting internal secretions and metabolic functions.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hye-Kyung Choi ◽  
Eun-Kyung Won ◽  
Young Pyo Jang ◽  
Se-Young Choung

The antiobesity effects ofCodonopsis lanceolata(CL) were evaluated in a high-calorie/high-fat-diet (HFD-) induced obesity rat model and 3T3-L1 cells. The Sprague-Dawley male rats were fed a normal diet (ND) or a HFD for a period of 12 weeks. The rats were subdivided into groups: ND, ND + wildCodonopsis lanceolata(wCL) (900 mg/kg/day, p.o.), ND + cultivatedCodonopsis lanceolata(cCL) (900 mg/kg/day, p.o.), HFD, HFD + wCL (100, 300, or 900 mg/kg/day, p.o.), HFD + cCL (100, 300, or 900 mg/kg/day, p.o.), and HFD + sibutramine. The body weight gains of the administered HFD + CL (wCL or CCL) were lower than those of the rats fed with only the HFD group. Moreover, the weight of adipose pads and the serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol in the group administered HDL + CL were significantly lower than in the HFD group. The inhibitory effect of lipid accumulation in 3T3-L1 cells was measured by Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). Treatment of 3T3-L1 cells with wCL inhibited lipid accumulation and expression of C/EBPαand PPARγ. These results suggest that CL has a great potential as a functional food with anti-obesity effects and as a therapeutic alternative in the treatment of obesity.


Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3286
Author(s):  
Jiali Wei ◽  
Yiran Zhao ◽  
Chen Zhou ◽  
Qing Zhao ◽  
Hongqian Zhong ◽  
...  

Previous studies have suggested that polysaccharide from Enteromorpha clathrata (ECP) could be used as a potential prebiotic to treat dysbiosis-associated diseases. However, whether it has any therapeutic effects on obesity has not been investigated. In the present study, we explored the anti-obesity effect of ECP and illustrated that it can significantly reduce the body weight and decrease the serum levels of triacylglycerol and cholesterol in high-fat diet (HFD)-fed mice. As revealed by 16S rRNA high-throughput sequencing and bioinformatic analysis, HFD remarkably changed the composition of the gut microbiota and promoted the growth of opportunistic pathogens such as Mucispirillum, Desulfobacterota and Alphaproteobacteria in obese mice. Interestingly, ECP improved intestinal dysbiosis caused by HFD and reshaped the structure of the gut microbiota in diseased mice by increasing the abundance of butyrate-producing bacterium, Eubacterium xylanophilum, in the gut. Altogether, we demonstrate for the first time an anti-obesity effect of ECP and shed new light into its therapeutic mechanisms from the perspective of gut microbiota. Our study will pave the way for the development of ECP as new prebiotic for the treatment of obesity and its associated disorders.


Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 110
Author(s):  
Thorhildur Ditta Valsdottir ◽  
Bente Øvrebø ◽  
Thea Martine Falck ◽  
Sigbjørn Litleskare ◽  
Egil Ivar Johansen ◽  
...  

We assessed the effect of weight-loss induced with a low-carbohydrate-high-fat diet with and without exercise, on body-composition, cardiorespiratory fitness and cardiovascular risk factors. A total of 57 overweight and obese women (age 40 ± 3.5 years, body mass index 31.1 ± 2.6 kg∙m−2) completed a 10-week intervention using a low-carbohydrate-high-fat diet, with or without interval exercise. An equal deficit of 700 kcal∙day−1 was prescribed, restricting diet only, or moderately restricting diet and adding exercise, producing four groups; normal diet (NORM); low-carbohydrate-high-fat diet (LCHF); normal diet and exercise (NORM-EX); and low-carbohydrate-high-fat diet and exercise (LCHF-EX). Linear Mixed Models were used to assess between-group differences. The intervention resulted in an average 6.7 ± 2.5% weight-loss (p < 0.001). Post-intervention % fat was lower in NORM-EX than NORM (40.0 ± 4.2 vs. 43.5 ± 3.5%, p = 0.024). NORM-EX reached lower values in total cholesterol than NORM (3.9 ± 0.6 vs. 4.7 ± 0.7 mmol/L, p = 0.003), and LCHF-EX (3.9 ± 0.6 vs. 4.9 ± 1.1 mmol/L, p = 0.004). Post intervention triglycerides levels were lower in NORM-EX than NORM (0.87 ± 0.21 vs. 1.11 ± 0.34 mmol/L, p = 0.030). The low-carbohydrate-high-fat diet had no superior effect on body composition, V˙O2peak or cardiovascular risk factors compared to a normal diet, with or without exercise. In conclusion, the intervention decreased fat mass, but exercise improved body composition and caused the most favorable changes in total cholesterol and triglycerides in the NORM-EX. Exercise increased cardiorespiratory fitness, regardless of diet.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lisa R Beutler ◽  
Timothy V Corpuz ◽  
Jamie S Ahn ◽  
Seher Kosar ◽  
Weimin Song ◽  
...  

Body weight is regulated by interoceptive neural circuits that track energy need, but how the activity of these circuits is altered in obesity remains poorly understood. Here we describe the in vivo dynamics of hunger-promoting AgRP neurons during the development of diet-induced obesity in mice. We show that high-fat diet attenuates the response of AgRP neurons to an array of nutritionally-relevant stimuli including food cues, intragastric nutrients, cholecystokinin and ghrelin. These alterations are specific to dietary fat but not carbohydrate or protein. Subsequent weight loss restores the responsiveness of AgRP neurons to exterosensory cues but fails to rescue their sensitivity to gastrointestinal hormones or nutrients. These findings reveal that obesity triggers broad dysregulation of hypothalamic hunger neurons that is incompletely reversed by weight loss and may contribute to the difficulty of maintaining a reduced weight.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 352 ◽  
Author(s):  
Youngji Han ◽  
Haryung Park ◽  
Bo-Ra Choi ◽  
Yosep Ji ◽  
Eun-Young Kwon ◽  
...  

Recently, there has been a global shift in diet towards an increased intake of energy-dense foods that are high in sugars. D-allulose has received attention as a sugar substitute and has been reported as one of the anti-obesity food components; however, its correlation with the intestinal microbial community is not yet completely understood. Thirty-six C57BL/6J mice were divided in to four dietary groups and fed a normal diet (ND), a high-fat diet (HFD, 20% fat, 1% cholesterol, w/w), and a HFD with 5% erythritol (ERY) and D-allulose (ALL) supplement for 16 weeks. A pair-feeding approach was used so that all groups receiving the high-fat diet would have the same calorie intake. As a result, body weight and body fat mass in the ALL group were significantly decreased toward the level of the normal group with a simultaneous decrease in plasma leptin and resistin. Fecal short-chain fatty acid (SCFA) production analysis revealed that ALL induced elevated total SCFA production compared to the other groups. Also, ALL supplement induced the change in the microbial community that could be responsible for improving the obesity based on 16S rRNA gene sequence analysis, and ALL significantly increased the energy expenditure in Day(6a.m to 6pm). Taken together, our findings suggest that 5% dietary ALL led to an improvement in HFD-induced obesity by altering the microbiome community.


2021 ◽  
Author(s):  
Bende Liu ◽  
Xiaoling Liu ◽  
Ze Zhang ◽  
Yan Qin ◽  
Fang Zou ◽  
...  

Abstract Objective: To investigate the effects of tea blend composed of Enshi selenium-rich tea, gynostemma pentaphyllum and apenma on blood lipid and lipid metabolism in mice with hyperlipidemia and prevention of hyperlipidemia in mice on the high-fat diet.Methods: Mice were randomized into 7 groups, among which 6 groups were fed with high-fat diet to establish a hyperlipidemia mouse model, and the other group was fed with normal diet as the normal control. After the hyperlipidemia model was established, mice were fed with normal diet while receiving different regimens. The normal diet group, the high-fat control group and the positive control group were given physiological saline solution, physiological saline solution and atorvastatin daily by gavage, respectively. The initial intervention group was given medium dose tea blend solution by gavage, and the other three groups were given low, medium and high dose of tea solution daily by gavage, respectively. After 4 weeks of treatment, mice were sacrificed, blood samples were taken for monitoring of lipid metabolism, -liver and tissue tissues were removed for examination of morphology and gene expression.Results: The tea blend not only significantly reduced the level of blood lipid in hyperlipidemia mice, but also effectively protected the liver and kidney function (P < 0.05). Observation under the light microscope reveled that, high-fat diet led to the accumulation of fat in hepatocytes and disorder of hepatic cordage, while the tea blend alleviated the hepatocyte steatosis. In addition, the tea blend promoted the expression of HL and HSL genes, and increased the levels of LAXR and PPARA, which regulated lipid metabolism at the genetic level (P < 0.05).Conclusion: This study confirmed that drinking tea blend composed of Enshi selenium-enriched tea, Gynostemma pentaphyllum and Apocynum venetum could lower blood lipids in mice with hyperlipidemia. In addition, various doses of tea blend could be used for hyperlipidemia with good liver and kidney function, and medium or high dose of tea blend was relatively safe for hyperlipidemia with poor liver and kidney function.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wanpitak Pongkan ◽  
KEWARIN JINAWONG ◽  
Siriporn Chattipakorn ◽  
Nipon CHATTIPAKORN

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.


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