Duodenojejunal Bypass Plus Sleeve Gastrectomy Reduces Infiltration of Macrophages and Secretion of TNF-α in the Visceral White Adipose Tissue of Goto-Kakizaki Rats

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.

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Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

Nutrients ◽

10.3390/nu11010110 ◽

2019 ◽

Vol 11 (1) ◽

pp. 110 ◽

Cited By ~ 2

Author(s):

Luana Amorim Biondo ◽

Alexandre Abilio S. Teixeira ◽

Loreana S. Silveira ◽

Camila O. Souza ◽

Raquel G. F. Costa ◽

...

Keyword(s):

Colorectal Cancer ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Colon Carcinogenesis ◽

Serum Glucose ◽

Control Group ◽

Chow Diet ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha

Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation.

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NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00076.2004 ◽

2004 ◽

Vol 287 (2) ◽

pp. E331-E339 ◽

Cited By ~ 82

Author(s):

Muhammad R. Peeraully ◽

John R. Jenkins ◽

Paul Trayhurn

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Sympathetic Neurons ◽

Mrna Levels ◽

Rt Pcr ◽

White Adipocytes ◽

Pparγ Agonist ◽

Tnf Α ◽

Ngf Gene

The sympathetic nervous system plays a central role in lipolysis and the production of leptin in white adipose tissue (WAT). In this study, we have examined whether nerve growth factor (NGF), a target-derived neurotropin that is a key signal in the development and survival of sympathetic neurons, is expressed and secreted by white adipocytes. NGF mRNA was detected by RT-PCR in the major WAT depots of mice (epididymal, perirenal, omental, mesenteric, subcutaneous) and in human fat (subcutaneous, omental). In mouse WAT, NGF expression was observed in mature adipocytes and in stromal vascular cells. NGF expression was also evident in 3T3-L1 cells before and after differentiation into adipocytes. NGF protein, measured by ELISA, was secreted from 3T3-L1 cells, release being higher before differentiation. Addition of the sympathetic agonists norepinephrine, isoprenaline, or BRL-37344 (β3-agonist) led to falls in NGF gene expression and secretion by 3T3-L1 adipocytes, as did IL-6 and the PPARγ agonist rosiglitazone. A substantial decrease in NGF expression and secretion occurred with dexamethasone. In contrast, LPS increased NGF mRNA levels and NGF secretion. A major increase in NGF mRNA level (9-fold) and NGF secretion (≤40-fold) in 3T3-L1 adipocytes occurred with TNF-α. RT-PCR showed that the genes encoding the p75 and trkA NGF receptors were expressed in mouse WAT. These results demonstrate that white adipocytes secrete NGF (an adipokine), NGF synthesis being influenced by several factors with TNF-α having a major stimulatory effect. We suggest that NGF is a target-derived neurotropin and an inflammatory response protein in white adipocytes.

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SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging

Biomedicines ◽

10.3390/biomedicines8110514 ◽

2020 ◽

Vol 8 (11) ◽

pp. 514

Author(s):

Jennifer R. Matthews ◽

Lakshini Y. Herat ◽

Aaron L. Magno ◽

Shelley Gorman ◽

Markus P. Schlaich ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

White Adipose Tissue ◽

Sglt2 Inhibitor ◽

Mrna Levels ◽

Significant Elevation ◽

Sodium Glucose Cotransporter ◽

Tnf Α ◽

Significant Difference ◽

Reduce Weight Gain

Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT. Furthermore, we demonstrate that 2 weeks of Dapagliflozin treatment increases SNS innervation in WAT of hypertensive mice. This increase is accompanied by a non-significant elevation in mRNA levels of the Ucp1 and Pgc-1α genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators Il-6 and Tnf-α were detected in WAT of Dapagliflozin treated mice. These findings suggest that SGLT-2 inhibitor-associated prevention of weight gain may be mediated, at least in part, by inducing the beiging of WAT.

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White Adipose Tissue Production and Release of IL-6 and TNF-α Do Not Parallel Circulating and Cerebrospinal Fluid Concentrations in Pregnant Rats

Hormone and Metabolic Research ◽

10.1055/s-2008-1062701 ◽

2008 ◽

Vol 40 (6) ◽

pp. 375-380 ◽

Cited By ~ 5

Author(s):

S. Caja ◽

M. Puerta

Keyword(s):

Cerebrospinal Fluid ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Pregnant Rats ◽

Tnf Α ◽

Tissue Production

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Edible red seaweed Campylaephora hypnaeoides J. Agardh alleviates obesity and related metabolic disorders in mice by suppressing oxidative stress and inflammatory response

Nutrition & Metabolism ◽

10.1186/s12986-021-00633-5 ◽

2022 ◽

Vol 19 (1) ◽

Author(s):

Shigeru Murakami ◽

Chihiro Hirazawa ◽

Rina Yoshikawa ◽

Toshiki Mizutani ◽

Takuma Ohya ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

White Adipose Tissue ◽

Metabolic Disorders ◽

Serum Levels ◽

Diet Group ◽

Raw264.7 Cells ◽

Edible Seaweed ◽

Tnf Α

Abstract Background The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice. Methods Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells. Results Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, hyperglycemia, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-α, and interleukin-6 (IL-6) levels, while it decreased glutathione and superoxide dismutase. These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-α in macrophage RAW264.7 cells. Conclusions The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, hyperglycemia, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides.

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Adipose Tissue and Brain Metabolic Responses to Western Diet—Is There a Similarity between the Two?

International Journal of Molecular Sciences ◽

10.3390/ijms21030786 ◽

2020 ◽

Vol 21 (3) ◽

pp. 786 ◽

Cited By ~ 4

Author(s):

Arianna Mazzoli ◽

Maria Stefania Spagnuolo ◽

Cristina Gatto ◽

Martina Nazzaro ◽

Rosa Cancelliere ◽

...

Keyword(s):

Adipose Tissue ◽

Frontal Cortex ◽

White Adipose Tissue ◽

Insulin Signaling ◽

Metabolic Response ◽

Western Diet ◽

Dietary Fats ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha

Dietary fats and sugars were identified as risk factors for overweight and neurodegeneration, especially in middle-age, an earlier stage of the aging process. Therefore, our aim was to study the metabolic response of both white adipose tissue and brain in middle aged rats fed a typical Western diet (high in saturated fats and fructose, HFF) and verify whether a similarity exists between the two tissues. Specific cyto/adipokines (tumor necrosis factor alpha (TNF-α), adiponectin), critical obesity-inflammatory markers (haptoglobin, lipocalin), and insulin signaling or survival protein network (insulin receptor substrate 1 (IRS), Akt, Erk) were quantified in epididymal white adipose tissue (e-WAT), hippocampus, and frontal cortex. We found a significant increase of TNF-α in both e-WAT and hippocampus of HFF rats, while the expression of haptoglobin and lipocalin was differently affected in the various tissues. Interestingly, adiponectin amount was found significantly reduced in e-WAT, hippocampus, and frontal cortex of HFF rats. Insulin signaling was impaired by HFF diet in e-WAT but not in brain. The above changes were associated with the decrease in brain derived neurotrophic factor (BDNF) and synaptotagmin I and the increase in post-synaptic protein PSD-95 in HFF rats. Overall, our investigation supports for the first time similarities in the response of adipose tissue and brain to Western diet.

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