Lactococcus chungangensis CAU 28 alleviates diet-induced obesity and adipose tissue metabolism in vitro and in mice fed a high-fat diet

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

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Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice

Cell Death and Disease ◽

10.1038/s41419-021-03519-9 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xinhui Wang ◽

Yinan Zhao ◽

Dekun Zhou ◽

Yingpu Tian ◽

Gensheng Feng ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Scaffolding Protein ◽

Regulation Mechanism ◽

Standard Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Relevant Regulation

AbstractObesity is caused by a long-term imbalance between energy intake and consumption and is regulated by multiple signals. This study investigated the effect of signaling scaffolding protein Gab2 on obesity and its relevant regulation mechanism. Gab2 knockout (KO) and wild-type (WT) mice were fed with a standard diet (SD) or high-fat diet (HFD) for 12 weeks. The results showed that the a high-fat diet-induced Gab2 expression in adipose tissues, but deletion of Gab2 attenuated weight gain and improved glucose tolerance in mice fed with a high-fat diet. White adipose tissue and systemic inflammations were reduced in HFD-fed Gab2 deficiency mice. Gab2 deficiency increased the expression of Ucp1 and other thermogenic genes in brown adipose tissue. Furthermore, the regulation of Gab2 on the mature differentiation and function of adipocytes was investigated in vitro using primary or immortalized brown preadipocytes. The expression of brown fat-selective genes was found to be elevated in differentiated adipocytes without Gab2. The mechanism of Gab2 regulating Ucp1 expression in brown adipocytes involved with its downstream PI3K (p85)-Akt-FoxO1 signaling pathway. Our research suggests that deletion of Gab2 suppresses diet-induced obesity by multiple pathways and Gab2 may be a novel therapeutic target for the treatment of obesity and associated complications.

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Mechanism of SEMA3G knockdown-mediated attenuation of high-fat diet-induced obesity

Journal of Endocrinology ◽

10.1530/joe-19-0029 ◽

2020 ◽

Vol 244 (1) ◽

pp. 223-236 ◽

Cited By ~ 2

Author(s):

Min Liu ◽

Shuo Xie ◽

Weiwei Liu ◽

Jingjin Li ◽

Chao Li ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

High Fat Diet ◽

Adipocyte Differentiation ◽

Plasma Concentrations ◽

Axonal Guidance ◽

High Fat ◽

Diet Induced Obesity ◽

Primary Mouse

Obesity is a worldwide health problem. Semaphorins are involved in axonal guidance; however, the role of secretory semaphorin 3G (SEMA3G) in regulating adipocyte differentiation remains unclear. Microarray analysis showed that the SEMA3G gene was upregulated in an in vitro model of adipogenesis. In this study, SEMA3G was highly expressed in the white adipose tissue and liver. Analysis of 3T3-L1 cell and primary mouse preadipocyte differentiation showed that SEMA3G mRNA and protein levels were increased during the middle stage of cell development. In vitro experiments also showed that adipocyte differentiation was promoted by SEMA3G; however, SEMA3G inhibition using a recombinant lentiviral vector expressing a specific shRNA showed the opposite results. Mice were fed a chow or high-fat diet (HFD); knockdown of SEMA3G was found to inhibit weight gain, reduce fat mass in the tissues, prevent lipogenesis in the liver tissue, reduce insulin resistance and ameliorate glucose tolerance in HFD mice. Additionally, the effect of SEMA3G on HFD-induced obesity was activated through PI3K/Akt/GSK3β signaling in the adipose tissue and the AMPK/SREBP-1c pathway in the liver. Moreover, the plasma concentrations of SEMA3G and leptin were measured in 20 obese and 20 non-obese human subjects. Both proteins were increased in obese subjects, who also exhibited a lower level of adiponectin and presented with insulin resistance. In summary, we demonstrated that SEMA3G is an adipokine essential for adipogenesis, lipogenesis, and insulin resistance and is associated with obesity. SEMA3G inhibition may, therefore, be useful for treating diet-induced obesity and its complications.

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Inhibitory Effects of Fermented Ougan (Citrus reticulata cv. Suavissima) Juice on High-Fat Diet-induced Obesity Associated with White Adipose Tissue Browning and Gut Microbiota Modulation in Mice

Food & Function ◽

10.1039/d0fo03423a ◽

2021 ◽

Author(s):

Xiao Guo ◽

Xuedan Cao ◽

Xiugui Fang ◽

Ailing Guo ◽

Erhu Li

Keyword(s):

Adipose Tissue ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Gut Microbiota ◽

High Fat Diet ◽

Citrus Reticulata ◽

Inhibitory Effects ◽

High Fat ◽

Diet Induced Obesity ◽

Tissue Browning

In this study, Ougan juice (OJ) and lactic acid bacteria fermented Ougan juice (FOJ) were investigated individually for their capability of preventing obesity in high-fat diet (HFD)-fed C57BL/6J mice. After...

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Trans-palmitoleic Acid Reduces Adiposity via Increased Lipolysis in a Rodent Model of Diet-Induced Obesity

British Journal Of Nutrition ◽

10.1017/s0007114521001501 ◽

2021 ◽

pp. 1-24

Author(s):

L. Irasema Chávaro-Ortiz ◽

Brenda D. Tapia-Vargas ◽

Mariel Rico-Hidalgo ◽

Ruth Gutiérrez-Aguilar ◽

María E. Frigolet

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Visceral Adipose Tissue ◽

High Fat Diet ◽

Palmitoleic Acid ◽

Rodent Model ◽

Adipocyte Size ◽

High Fat ◽

Diet Induced Obesity ◽

Visceral Adipose

Abstract Obesity is defined as increased adiposity, which leads to metabolic disease. The growth of adipose tissue depends on its capacity to expand, through hyperplasia or hypertrophy, in order to buffer energy surplus. Also, during the establishment of obesity, adipose tissue expansion reflects adipose lipid metabolism (lipogenesis and/or lipolysis). It is well known that dietary factors can modify lipid metabolism promoting or preventing the development of metabolic abnormalities that concur with obesity. Trans-palmitoleic acid (TP), a biomarker of dairy consumption, has been associated with reduced adiposity in clinical studies. Thus, we aimed to evaluate the effect of TP over adiposity and lipid metabolism-related genes in a rodent model of diet-induced obesity (DIO). To fulfil this aim, we fed C57BL/6 mice with a Control or a High Fat diet, added with or without TP (3g/kg diet), during 11 weeks. Body weight and food intake were monitored, fat pads were weighted, histology of visceral adipose tissue was analysed, and lipid metabolism-related gene expression was explored by qPCR. Results show that TP consumption prevented weight gain induced by high fat diet, reduced visceral adipose tissue weight, and adipocyte size, while increasing the expression of lipolytic molecules. In conclusion, we show for the first time that TP influences adipose tissue metabolism, specifically lipolysis, resulting in decreased adiposity and reduced adipocyte size in a DIO mice model.

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Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

Scientific Reports ◽

10.1038/s41598-020-80940-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maki Murakoshi ◽

Tomohito Gohda ◽

Eri Adachi ◽

Saki Ichikawa ◽

Shinji Hagiwara ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Kidney Injury ◽

Proximal Tubules ◽

Tubular Damage ◽

Standard Diet ◽

Mrna Levels ◽

High Fat ◽

Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

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Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance

British Journal of Pharmacology ◽

10.1111/bph.14802 ◽

2019 ◽

Vol 176 (20) ◽

pp. 3983-4001 ◽

Cited By ~ 8

Author(s):

Shengnan Shen ◽

Qiwen Liao ◽

Tian Zhang ◽

Ruile Pan ◽

Ligen Lin

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity

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Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

British Journal Of Nutrition ◽

10.1017/s0007114511006209 ◽

2011 ◽

Vol 108 (6) ◽

pp. 1025-1033 ◽

Cited By ~ 7

Author(s):

Sumithra Urs ◽

Terry Henderson ◽

Phuong Le ◽

Clifford J. Rosen ◽

Lucy Liaw

Keyword(s):

Adipose Tissue ◽

Bone Loss ◽

Bone Mass ◽

Body Fat ◽

High Fat Diet ◽

Conditional Knockout ◽

Whole Body ◽

High Fat ◽

Tissue Specific ◽

Diet Induced Obesity

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

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