• IMMUNE NETWORK
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• v.11 no.1
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• pp.59-67
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• 2011

Background: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-$1{\beta}$, -6, -12, TNF-${\alpha}$) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and $11{\beta}$-HSD1 both in the liver and WAT. Conclusion: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on $PPAR{\gamma}$ and $11{\beta}$-HSD1 ression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.

• Molecules and Cells
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• v.43 no.5
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• pp.431-437
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• 2020

The hypothalamus is a crucial organ for the maintenance of appropriate body fat storage. Neurons in the hypothalamic arcuate nucleus (ARH) detect energy shortage or surplus via the circulating concentrations of metabolic hormones and nutrients, and then coordinate energy intake and expenditure to maintain energy homeostasis. Malfunction or loss of hypothalamic ARH neurons results in obesity. Accumulated evidence suggests that hypothalamic inflammation is a key pathological mechanism that links chronic overconsumption of a high-fat diet (HFD) with the development of obesity and related metabolic complications. Interestingly, overnutrition-induced hypothalamic inflammation occurs specifically in the ARH, where microglia initiate an inflammatory response by releasing proinflammatory cytokines and chemokines in response to excessive fatty acid flux. Upon more prolonged HFD consumption, astrocytes and perivascular macrophages become involved and sustain hypothalamic inflammation. ARH neurons are victims of hypothalamic inflammation, but they may actively participate in hypothalamic inflammation by sending quiescence or stress signals to surrounding glia. In this mini-review, we describe the current state of knowledge regarding the contributions of neurons and glia, and their interactions, to HFD-induced hypothalamic inflammation.

• Nutrition Research and Practice
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• v.10 no.6
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.13.1-13.14
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• 2022

Chronic inflammation plays a critical role in the development of obesity-associated metabolic disorders such as insulin resistance. Obesity alters the microenvironment of adipose tissue and the intestines from anti-inflammatory to pro-inflammatory, which promotes low grade systemic inflammation and insulin resistance in obese mice. Various T cell subsets either help maintain metabolic homeostasis in healthy states or contribute to obesity-associated metabolic syndromes. In this review, we will discuss the T cell subsets that reside in adipose tissue and intestines and their role in the development of obesity-induced systemic inflammation.

• Nutrition Research and Practice
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• v.14 no.5
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• pp.425-437
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• 2020

BACKGROUND/OBJECTIVES: Different fatty acids exert different health benefits. This study investigated the potential protective effects of perilla, olive, and safflower oils on high-fat diet-induced obesity and colon inflammation. MATERIALS/METHODS: Five-week old, C57BL/6J mice were assigned to 5 groups: low-fat diet (LFD), high-fat diet (HFD) and high-fat diet supplemented with-perilla oil (HPO), olive oil (HOO), and safflower oil (HSO). After 16 weeks of the experimental period, the mice were sacrificed, and blood and tissues were collected. The serum was analyzed for obesity- and inflammation-related biomarkers. Gene expression of the biomarkers in the liver, adipose tissue, and colon tissue was analyzed. Micro-computed tomography (CT) analysis was performed one week before sacrifice. RESULTS: Treatment with all the three oils significantly improved obesity-induced increases in body weight, liver weight, and epididymal fat weight as well as serum triglyceride and leptin levels. Treatment with perilla oil (PO) and safflower oil (SO) increased adiponectin levels. The micro-CT analysis revealed that PO and SO reduced abdominal fat volume considerably. The mRNA expression of lipogenic genes was reduced in all the three oilsupplemented groups and PO upregulated lipid oxidation in the liver. Supplementation of oils improved macroscopic score, increased colon length, and decreased serum endotoxin and proinflammatory cytokine levels in the colon. The abundance of Bifidobacteria was increased and that of Enterobacteriaceae was reduced in the PO-supplemented group. All three oils reduced proinflammatory cytokine levels, as indicated by the mRNA expression. In addition, PO increased the expression of tight junction proteins. CONCLUSIONS: Taken together, our data indicate that the three oils exert similar anti-obesity effects. Interestingly, compared with olive oil and SO, PO provides better protection against high-fat diet-induced colon inflammation, suggesting that PO consumption helps manage inflammation-related diseases and provides omega-3 fatty acids needed by the body.

• Molecules and Cells
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• v.47 no.3
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• pp.100007.1-100007.11
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• 2024

Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46⁺ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesityinduced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

• ALGAE
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• v.38 no.1
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• pp.81-92
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• 2023

Obesity-induced inflammation is crucial in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we investigated the effects of the Gracilaria chorda (GC) on lipid accumulation and obesity-induced inflammatory changes or glucose homeostasis in cell models (3T3-L1 adipocytes and RAW 264.7 macrophages). Samples of GC were extracted using solvents (water, methanol, and ethanol) and subcritical water (SW) at different temperatures (90, 150, and 210℃). The total phenolic content of GCSW extract at 210℃ (GCSW210) showed the highest content compared to others, and GCSW210 highly inhibited lipid accumulation and significantly reduced gene expressions of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein-1c, and fatty acid synthase in 3T3-L1 adipocytes. In addition, GCSW210 effectively downregulated the pro-inflammatory cytokine regulator pathways in RAW 264.7 macrophages, including mitogen-activated protein kinase, signal transducers and activators of transcription and nuclear factor-κB. In co-culture of 3T3-L1 adipocytes and RAW 264.7 macrophages, GCSW210 significantly reduced nitric oxide production and interleukin-6 levels, and improved glucose uptake with dose-dependent manner. These findings suggest that GCSW210 improves glucose metabolism by attenuating obesity-induced inflammation in adipocytes, which may be used as a possible treatment option for managing obesity and associated metabolic disorders.

• IMMUNE NETWORK
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• v.11 no.2
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• pp.107-113
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• 2011

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• BMB Reports
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• v.55 no.10
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• pp.500-505
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• 2022

Uncoupling protein 2 (Ucp2) was first introduced as a member of Uncoupling protein family and a regulator of ROS formation; however, its role in adipose tissue is not fully understood. In the present study, we have investigated the role of Ucp2 against high-fat diet (HFD)-induced obesity in epididymal white adipose tissue (eWAT) and browning of inguinal white adipose tissue (iWAT). Diet-induced obesity is closely related to macrophage infiltration and the secretion of pro-inflammatory cytokines. Macrophages surround adipocytes and form a crown-like-structure (CLS). Some reports have suggested that CLS formation requires adipocyte apoptosis. After 12 weeks of HFD challenge, Ucp2 knockout (KO) mice maintained relatively lean phenotypes compared to wild-type (WT) mice. In eWAT, macrophage infiltration, CLS formation, and inflammatory cytokines were reduced in HFD KO mice compared to HFD WT mice. Surprisingly, we found that apoptotic signals were also reduced in the Ucp2 KO mice. Our study suggests that Ucp2 deficiency may prevent diet-induced obesity by regulating adipocyte apoptosis. However, Ucp2 deficiency did not affect the browning capacity of iWAT.