Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice

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.

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Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

Scientific Reports ◽

10.1038/s41598-021-90952-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Safia Akhtar ◽

Silas A. Culver ◽

Helmy M. Siragy

Keyword(s):

Protein Expression ◽

High Fat Diet ◽

Normal Diet ◽

Receptor Expression ◽

Wild Type ◽

High Fat ◽

Renal Gluconeogenesis ◽

Mrna And Protein Expression ◽

Polymerase Chain ◽

Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

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

Biochemical Journal ◽

10.1042/bcj20210100 ◽

2021 ◽

Author(s):

Sathish Sivaprakasam ◽

Sabarish Ramachandran ◽

Mohd Omar Faruk Sikder ◽

Yangzom Doma Bhutia ◽

Mitchell Wachtel ◽

...

Keyword(s):

Weight Loss ◽

High Fat Diet ◽

Amino Acid Profile ◽

Normal Diet ◽

The Body ◽

Multiple Models ◽

High Fat ◽

Liver And Kidney ◽

Obesity In Mice ◽

Treatment Of Obesity

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.

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Effects of Hwangryunjihwang-tang on In Vitro Fertilization and Ovulation in Mice Fed a High-fat Diet

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03000904 ◽

2003 ◽

Vol 31 (02) ◽

pp. 213-223

Author(s):

H. G. Choi ◽

D. H. Kwak ◽

J. Y. Kim ◽

Y. J. Choi ◽

B. S. Kil ◽

...

Keyword(s):

Body Weight ◽

Embryonic Development ◽

High Fat Diet ◽

Normal Diet ◽

The Body ◽

High Fat ◽

Reproductive Dysfunction ◽

Vitro Fertilization

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.

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Antiobesity Effect ofCodonopsis lanceolatain High-Calorie/High-Fat-Diet-Induced Obese Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/210297 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 16

Author(s):

Hye-Kyung Choi ◽

Eun-Kyung Won ◽

Young Pyo Jang ◽

Se-Young Choung

Keyword(s):

Lipid Accumulation ◽

High Fat Diet ◽

Density Lipoprotein ◽

Normal Diet ◽

The Body ◽

Male Rats ◽

Sprague Dawley ◽

High Fat ◽

Codonopsis Lanceolata ◽

High Calorie

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.

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Hypolipidemic Effects of Three Purgative Decoctions

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep178 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Sung-Hui Tseng ◽

Ting-Yi Chien ◽

Jiun-Rong Chen ◽

I-Hsin Lin ◽

Ching-Chiung Wang

Keyword(s):

High Fat Diet ◽

Weight Control ◽

Internal Heat ◽

Serum Triglyceride ◽

Hepatic Function ◽

The Body ◽

Lipid Lowering ◽

High Fat ◽

Beneficial Effects ◽

Lipid Lowering Effect

In traditional Chinese medicine (TCM), purgation is indicated when a person suffers an illness due to the accumulation of evil internal heat. Obese individuals with a large belly, red face, thick and yellow tongue fur, constipation, and avoidance of heat are thought accumulates of evil internal heat, and they are also treated with purgatives such asTa-Cheng-Chi-Tang(TCCT),Xiao-Chen-Chi-Tang(XCCT), andTiao-Wei-Chen-Chi-Tang(TWCCT) by TCM doctors. In previous studies, our group found that TCCT has potent anti-inflammatory activity, and that XCCT is an effective antioxidant. Since rhubarb is the principle herb in these three prescriptions, we will first present a thorough review of the literature on the demonstrated effect (or lack of effect) of rhubarb and rhubarb-containing polyherbal preparations on lipid and weight control. We will then continue our research with an investigation of the anti-obesity and lipid-lowering effect of TCCT, XCCT, TWCCT, and rhubarb extracts using two animal models. TWCCT lowered the serum triglyceride concentration as much as fenofibrate in Triton WR-1339-treated mice. Daily supplementation with XCCT and TWCCT significantly attenuated the high-fat-diet-induced hypercholesterolemia in rats. In addition, TWCCT also significantly lowered the high-fat-diet-induced hypertriglycemia. Although feeding high-fat diet rats with these extracts did not cause loose stools or diarrhea or other deleterious effects on renal or hepatic function. None of these extracts lowered the body weight of rats fed on high-fat diet. In conclusion, the results suggest that XCCT and TWCCT might exert beneficial effects in the treatment of hyperlipidemia.

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Djulis Hull Improves Insulin Resistance and Modulates the Gut Microbiota in High-Fat Diet (HFD)-Induced Hyperglycaemia

Antioxidants ◽

10.3390/antiox11010045 ◽

2021 ◽

Vol 11 (1) ◽

pp. 45

Author(s):

Yu-Tang Tung ◽

Jun-Lan Zeng ◽

Shang-Tse Ho ◽

Jin-Wei Xu ◽

I-Hsuan Lin ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Tolerance ◽

Gut Microbiota ◽

Protein Expression ◽

Crude Extract ◽

High Fat Diet ◽

Insulin Signalling ◽

Oral Glucose ◽

Model Assessment ◽

High Fat

In this study, we annotated the major flavonoid glycoside, rutin, of djulis hull crude extract using a Global Natural Products Social Molecular Networking (GNPS) library and its MS/MS spectra. To evaluate the protective effect of djulis hull crude extract and rutin on glucose tolerance, we fed mice a high-fat diet (HFD) for 16 weeks to induce hyperglycaemia. These results showed that crude extract significantly decreased HFD-induced elevation in the area under the curve (AUC) of weekly random blood glucose and oral glucose tolerance tests (OGTT), homeostasis model assessment (HOMA-IR), and advanced glycation end product (AGE) levels, and significantly increased pIRS1 and Glut4 protein expression in epididymal white adipose tissue (eWAT) and liver. Furthermore, the HFD-induced reduction in the activity of glutathione peroxidase (GPx) and catalase (CAT) was reversed by crude extract. In addition, ZO-1 and occludin protein expression in the colon was markedly downregulated in HFD-fed mice, resulting in decreased intestinal permeability and lipopolysaccharide (LPS) translocation, but were restored following crude extract. Moreover, the crude extract intervention had a profound effect on the alpha diversity and microbial community in the gut microbiota. Therefore, djulis hull crude extract could improve blood glucose and increase insulin receptor sensitivity in HFD-induced hyperglycaemia, which is likely due to its modulation of the gut microbiota, preservation of the integrity of the intestinal barrier to reduce body inflammation, increased antioxidant activity, and modulation of insulin signalling.

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PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-γ/CD36 Pathway

BioMed Research International ◽

10.1155/2017/8234507 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Yu Liu ◽

Fei Cheng ◽

Yuxuan Luo ◽

Zhu Zhan ◽

Peng Hu ◽

...

Keyword(s):

Hepatic Steatosis ◽

High Fat Diet ◽

Liver Lipid ◽

Serum Triglyceride ◽

The Body ◽

Chow Diet ◽

Therapeutic Effects ◽

Peroxisome Proliferator ◽

High Fat ◽

Curcumin Derivative

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.

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Schisandra Fruit Vinegar Lowers Lipid Profile in High-Fat Diet Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7083415 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Rui Yuan ◽

Guangren Sun ◽

Jiaqi Gao ◽

Zepeng Yu ◽

Chunyan Yu ◽

...

Keyword(s):

High Fat Diet ◽

Density Lipoprotein ◽

Serum Triglyceride ◽

Liver Weight ◽

The Body ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Heme Oxygenase 1 ◽

Related Factor ◽

High Fat

Hyperlipidemia and its associated obesity, hepatic steatosis, and NAFLD are worldwide problems. However, there is no ideal pharmacological treatment for these. Therefore, the complementary therapies that are both natural and safe have been focused. Healthy foods, such as fruit vinegar, may be one of the best choices. In this study, we made a special medicinal fruit vinegar, Schisandra fruit vinegar (SV), and examined its lipid-lowering effects and the underlying mechanisms in a high-fat diet rat model. The results showed that SV significantly reduced the body weight, liver weight, liver index, the serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), increased the content of high-density lipoprotein cholesterol (HDL-C) and the activity of superoxide dismutase (SOD), upregulated the expressions of peroxisome proliferative activated receptor (PPAR-α), peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), and carnitine palmitoyltransferase 1 (CPT1) proteins, increased the contents of key component of antioxidant defense NF-E2-related factor 2 (NRF2) and its downstream heme oxygenase-1 (HO-1) protein, and downregulated the expression of Kelch-like ECH-associated protein 1 (KEAP1). These results suggest that SV has weight loss and lipid-lowering effects in HFD rats, which may be related to its upregulation of the expressions of β-oxidation -elated PPAR-α, CPT1, and ACOX1 and the regulation of the expressions of antioxidant pathway-related KEAP1-NRF2-HO-1. Therefore, all these data provide an experimental basis for the development of SV as a functional beverage which is safe, effective, convenient, and inexpensive.

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Improvement on Lipid Metabolic Disorder by 3′-Deoxyadenosine in High-Fat-Diet-Induced Fatty Mice

The American Journal of Chinese Medicine ◽

10.1142/s0192415x10008470 ◽

2010 ◽

Vol 38 (06) ◽

pp. 1065-1075 ◽

Cited By ~ 5

Author(s):

Ya-Jing Niu ◽

Rong-Ya Tao ◽

Qian Liu ◽

Jin-Ying Tian ◽

Fei Ye ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

High Fat Diet ◽

Metabolic Disorder ◽

Tolerance Test ◽

The Body ◽

Oral Glucose ◽

Model Assessment ◽

High Fat ◽

Lipid Metabolic Disorder

This study explores the effects of 3′-deoxyadenosine, a compound from Cordyceps militaris, on lipid metabolic disorder induced by a high-fat-diet in C57BL/6 mice. These mice had an obese body, lipid metabolic disorder and insulin resistance and were treated orally with 100 mg/kg/day 3′-deoxyadenosine (DA), 15 mg/kg/day rosiglitazone and 150 mg/kg/day fenofibrate, respectively. Compared to the model mice, the body weight gain in DA-treated mice were decreased by 66.5%, serum triglyceride and total cholesterol levels were decreased by 20.7% and 16.7%, respectively, and the triglyceride content in the skeletal muscle was reduced by 41.2%. This treatment also had a significant effect on insulin resistance. In DA-treated mice, the serum insulin levels and homeostasis model assessment of the insulin resistance index were decreased by 30% and 46%, respectively, and the areas under the glucose-time curve were depressed by 18% in the insulin tolerance test and by 21.5% in the oral glucose tolerance test. Finally, the value of glucose infusion rates and insulin induced-glucose uptake into the skeletal muscle in the hyperinsulinemic-euglycemic clamp test were increased by 18% and 41%, respectively, compared to those in the model mice. This data suggests that the effects of DA on lipid metabolic disorder induced by a high-fat-diet may be linked to its improvement on insulin resistance, especially concerning the increase of insulin sensitivity in the skeletal muscle.

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Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats

Circulation ◽

10.1161/circ.142.suppl_3.15634 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Wanpitak Pongkan ◽

KEWARIN JINAWONG ◽

Siriporn Chattipakorn ◽

Nipon CHATTIPAKORN

Keyword(s):

Mitochondrial Function ◽

High Fat Diet ◽

Time Course ◽

Left Ventricular ◽

Normal Diet ◽

The Body ◽

Lv Function ◽

High Fat ◽

Lv Dysfunction

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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