Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization

Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE−/− mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1β levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1β, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.

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Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization

Integrative Cancer Therapies ◽

10.1177/1534735420949678 ◽

2020 ◽

Vol 19 ◽

pp. 153473542094967

Author(s):

Min Kyoon Kim ◽

Yesl Kim ◽

SeungHwa Park ◽

Eunju Kim ◽

Yerin Kim ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

High Fat Diet ◽

Tumor Volume ◽

Macrophage Polarization ◽

M2 Macrophage ◽

High Fat ◽

Low Intensity ◽

M2 Macrophage Polarization ◽

Low Intensity Exercise

Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.

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Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy

International Journal of Molecular Sciences ◽

10.3390/ijms19123903 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3903 ◽

Cited By ~ 10

Author(s):

Xiaofei Zhu ◽

Jingyi Yang ◽

Wenjuan Zhu ◽

Xiaoxiao Yin ◽

Beibei Yang ◽

...

Keyword(s):

Lipid Accumulation ◽

High Fat Diet ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Sirtuin 1 ◽

Lipid Lowering ◽

Low Density ◽

Lipoprotein Receptor ◽

High Fat ◽

Density Lipoprotein Receptor

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (25 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

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Hot Water Extract of Mulberry Leaf Ameliorates Hepatic Fat Accumulation and Inflammation in Rats Fed a High-Fat Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_048 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 415-415

Author(s):

Jibin Kim ◽

Chaemin Kim ◽

Mak-Soon Lee ◽

Hyunmi Ko ◽

Soojin Lee ◽

...

Keyword(s):

High Fat Diet ◽

Water Extract ◽

Density Lipoprotein ◽

Hot Water ◽

Mrna Levels ◽

High Fat ◽

Fat Accumulation ◽

Mulberry Leaf ◽

Hot Water Extract ◽

Hepatic Fat

Abstract Objectives This study was conducted to investigate the effect of mulberry leaf extract on hepatic fat accumulation and inflammation in rats fed a high-fat diet. Methods Male Sprague–Dawley rats were randomly divided into three groups. Each group fed normal diet (NOR), high-fat diet (HF), or HF supplemented with 0.8% (w/w) hot water extract of mulberry leaf (HF + ME) for 14 weeks. Results The mulberry extract (ME) supplementation reduced body weight and white adipose tissues (epididymal, retroperitoneal, and mesenteric) weights. Serum levels of triglyceride (TG), total cholesterol (TC), free fatty acids (FFAs), and low-density lipoprotein cholesterol (LDL-C) were lower, while high-density lipoprotein cholesterol (HDL-C) level was higher in the HF + ME group compared to the HF group. The ME reduced the hepatic total lipid, TG, and TC levels compared to the HF group. The mRNA levels of genes related to fatty acid synthesis, such as CD36, sterol regulatory element binding protein 1c (SREBP-1c), and fatty acid synthase (FAS) were down-regulated by the ME supplementation. In addition, the ME lowered the mRNA levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), compared to the HF group. The serum TNF-α level of the HF + ME group was significantly lower than that of the HF group. Conclusions These results suggested that the ME attenuated high-fat diet-induced hepatic fat accumulation and inflammation via regulating gene expression related to hepatic lipid metabolism and pro-inflammatory mediators. Therefore, it is postulated that the ME might be useful as a functional food ingredient to prevent obesity-induced hepatic fat accumulation and inflammation. Funding Sources None.

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High-Intensity Interval Training Reversed High-Fat Diet–Induced M1-Macrophage Polarization in Rat Adipose Tissue via Inhibition of NOTCH Signaling

Journal of Inflammation Research ◽

10.2147/jir.s237049 ◽

2020 ◽

Vol Volume 13 ◽

pp. 165-174 ◽

Cited By ~ 1

Author(s):

Mehrnoosh Shanaki ◽

Maryam Khosravi ◽

Arezoo Khoshdooni-Farahani ◽

Alireza Dadashi ◽

Mohammad Foad Heydari ◽

...

Keyword(s):

Adipose Tissue ◽

Notch Signaling ◽

High Fat Diet ◽

Macrophage Polarization ◽

Interval Training ◽

High Intensity Interval Training ◽

High Fat ◽

M1 Macrophage ◽

High Intensity Interval ◽

Rat Adipose Tissue

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Abstract 693: TLR3 Modulates Inflammation and Lipolysis in Visceral Adipose Tissue in High Fat Diet-fed Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.693 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Cuiqing Liu ◽

Guohua Lin ◽

Guoqing Zhang ◽

Huanhuan Wang ◽

Hongping Yin ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

High Fat Diet ◽

Dietary Factors ◽

Whole Body ◽

Mrna Levels ◽

High Fat ◽

M1 Macrophage ◽

Visceral Adipose ◽

Fat Feeding

Inflammation in insulin sensitive tissues, the visceral adipose tissue (VAT), is a central abnormality in obesity/insulin resistance (IR), with recruitment of innate immune cells such as monocytes into adipose tissue driving the development of glucose and lipoprotein dysregulation. We evaluated the role of Toll like receptor 3 (TLR3) in high fat diet-induced obesity and IR. Wild-type C57BL/6 and TLR3 -/- male mice were fed a high fat diet for 15 weeks. High fat feeding resulted in increased TLR3 expression in VAT. TLR3 deficiency attenuated the high fat diet-increased body weight, fasting blood glucose, whole body IR and impaired glucose tolerance. Morphologically, high fat diet induced adiposity and enlarged adipocyte area in VAT, which were attenuated in TLR3 -/- mice. Functionally, high fat diet induced dysregulation of adipocytokines such as downregulation of adiponectin and resistin, upregulation of leptin in VAT, with the disturbance of adiponectin and leptin was corrected in TLR3-/- mice. In addition, high fat diet inhibited insulin pathway, accompanied with decreased phosphorylation of AMPK and lowered expression of lipolysis-related enzymes such as HSL and ATGL, both at the mRNA levels and protein levels, all of which was corrected by TLR3 deficiency. Finally, TLR3 deletion suppressed the high fat feeding-mediated macrophage polarization, evidenced by increased type M1 macrophage (F4/80+/CD11c+/CD206-) infiltration and upregulation of M1 genes such as IL-6 and TNFα. TLR3 modulates high fat diet-induced IR and obesity by suppressing M1 macrophage-mediated VAT inflammation, facilitating secretion of adipocyte-derived hormones, thus enhanced AMPK activity and adipose lipolysis. These findings provide new mechanistic links between dietary factors-mediated IR and associated abnormalities in lipid metabolism and adipose inflammation.

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A High-Fat Diet Exacerbates the Course of Experimental Trypanosoma cruzi Infection That Can Be Mitigated by Treatment with Simvastatin

BioMed Research International ◽

10.1155/2020/1230461 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Débora Maria Soares de Souza ◽

Guilherme de Paula Costa ◽

Ana Luísa Junqueira Leite ◽

Daniela Silva de Oliveira ◽

Kelerson Mauro de Castro Pinto ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

High Fat Diet ◽

Biochemical Parameters ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Histopathological Analysis ◽

High Fat ◽

Inflammatory State

The protozoan Trypanosoma cruzi is responsible for triggering a damage immune response in the host cardiovascular system. This parasite has a high affinity for host lipoproteins and uses the low-density lipoprotein (LDL) receptor for its invasion. Assuming that the presence of LDL cholesterol in tissues could facilitate T. cruzi proliferation, dietary composition may affect the parasite-host relationship. Therefore, the aim of this study was to evaluate myocarditis in T. cruzi-infected C57BL/6 mice—acute phase—fed a high-fat diet and treated with simvastatin, a lipid-lowering medication. Animals (n=10) were infected with 5×103 cells of the VL-10 strain of T. cruzi and treated or untreated daily with 20 mg/kg simvastatin, starting 24 h after infection and fed with a normolipidic or high-fat diet. Also, uninfected mice, treated or not with simvastatin and fed with normolipidic or high-fat diet, were evaluated as control groups. Analyses to measure the production of chemokine (C-C motif) ligand 2 (CCL2), interferon- (IFN-) γ, interleukin- (IL-) 10, and tumor necrosis factor (TNF); total hepatic lipid dosage; cholesterol; and fractions, as well as histopathological analysis, were performed on day 30 using cardiac and fat tissues. Our results showed that the high-fat diet increased (i) parasite replication, (ii) fat accumulation in the liver, (iii) total cholesterol and LDL levels, and (iv) the host inflammatory state through the production of the cytokine TNF. However, simvastatin only reduced the production of CCL2 but not that of other inflammatory mediators or biochemical parameters. Together, our data suggest that the high-fat diet may have worsened the biochemical parameters of the uninfected and T. cruzi-infected animals, as well as favored the survival of circulating parasites.

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Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet–fed mice

Nutrition Research ◽

10.1016/j.nutres.2015.12.007 ◽

2016 ◽

Vol 36 (4) ◽

pp. 369-379 ◽

Cited By ~ 9

Author(s):

Jung-Woo Kang ◽

Jun-Kyu Shin ◽

Eun-Ji Koh ◽

Hyojeong Ryu ◽

Hyoung Ja Kim ◽

...

Keyword(s):

Hepatic Steatosis ◽

High Fat Diet ◽

Macrophage Polarization ◽

M2 Macrophage ◽

High Fat ◽

Opuntia Ficus Indica ◽

M2 Macrophage Polarization

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Lipid-lowering effect of molluscan (Katelysia opima) glycosaminoglycan (GAG) in hypercholesterolemic induced rats

Biological Chemistry ◽

10.1515/hsz-2013-0214 ◽

2014 ◽

Vol 395 (3) ◽

pp. 355-364 ◽

Cited By ~ 1

Author(s):

Vijayabaskar Pandian ◽

Natarajan Aravindan ◽

Sethupathy Subramanian ◽

Somasundaram T. Somasundaran

Keyword(s):

High Fat Diet ◽

Low Density Lipoprotein ◽

Cholesterol Acyltransferase ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Low Density ◽

High Fat ◽

Lecithin Cholesterol Acyltransferase ◽

Baseline Levels ◽

Lipid Lowering Effect

Abstract Identifying pharmacologically safe lipid-lowering ‘deliverables’ could potentiate therapeutic outcome for diet-induced atherogenesis. Accordingly, we investigated the potential of molluscan (Katelysia opima) glycosaminoglycan (GAG) in modulating the early lipid changes in atherogenesis. Wistar rats were fed a diet with (n=24) or without (n=6) hypercholesterolemic atherogenic CCT (rat chow supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) for 17 days. CCT-fed rates were (i) treated with isolated molluscan GAG (40 mg/kg/day, s.c.) for 10 days after the introduction of CCT diet, (ii) cotreated with GAG (40 mg/kg/day, s.c.) for 17 days, or (iii) treated with heparin (200 units/kg/day, s.c.) for 10 days after the introduction of CCT. The increases induced by CCT diet in the plasma levels of cholesterol, triglycerides, high-density lipoprotein, very-low-density lipoprotein, and low-density lipoprotein were completely attenuated with GAG treatment. Consistently, alterations induced by CCT diet in the levels of plasma lecithin cholesterol acyltransferase and lipoprotein lipase activities were restored to baseline levels with GAG treatment. Coherently, histology revealed a decrease associated with GAG treatment in the CCT-diet-induced foam cells (in aorta), tubular damages (kidney), and lipid accumulations (liver). Together, these results suggest that GAG may exert antiatherogenesis potential by significantly attenuating lipid modulations derived by a high-fat diet. Further, the data imply that the GAG extracts may comprehensively prevent hypercholesterolemia-associated tissue damage and could thus serve as a therapeutic deliverable for hypercholesterolemia.

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Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities

Journal of Translational Medicine ◽

10.1186/s12967-021-02727-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xinxin Zhang ◽

Yating Qin ◽

Xiaoning Wan ◽

Hao Liu ◽

Chao Lv ◽

...

Keyword(s):

Western Blot ◽

Inflammatory Cytokines ◽

Lipid Accumulation ◽

High Fat Diet ◽

Lipid Profiles ◽

Foam Cell Formation ◽

M2 Macrophage ◽

Polarization Conversion ◽

High Fat ◽

Raw264.7 Macrophages

Abstract Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE−/−) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages. Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE−/− mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

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