scholarly journals Adipose tissue transplantation ameliorates lipodystrophy-associated metabolic disorders in seipin-deficient mice

2019 ◽  
Vol 316 (1) ◽  
pp. E54-E62 ◽  
Author(s):  
Huan Wang ◽  
Peng-Fei Xu ◽  
Jing-Yi Li ◽  
Xue-Jing Liu ◽  
Xiao-Yue Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Metabolic Disorders ◽  
Tissue Transplantation ◽  
Hepatic Lipogenesis ◽  
Wild Type ◽  
Regulation Of Metabolism ◽  
Plasma Leptin ◽  
Deficient Mice

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue and can lead to hepatic steatosis, insulin resistance (IR), and dyslipidemia in humans. Adipose tissue secretes many adipokines that are central to the regulation of metabolism. In this study, we investigated whether transplantation of normal adipose tissue could ameliorate severe hepatic steatosis, IR, and dyslipidemia in lipoatrophic seipin knockout (SKO) mice. Normal adipose tissue from wild-type mice was transplanted into 6-wk-old SKO mice. At 4 mo after adipose tissue transplantation (AT), the transplanted fat survived with detectable blood vessels, and the reduced levels of plasma leptin, a major adipokine, were dramatically increased. Severe hepatic steatosis, IR, and dyslipidemia in SKO mice were ameliorated after AT. In addition, abnormal hepatic lipogenesis and β-oxidation gene expression in SKO mice were improved after AT. Our results suggest that AT may be an effective treatment to improve lipodystrophy-associated metabolic disorders.

scholarly journals Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db/db Mice

2019 ◽  
Vol 20 (9) ◽  
pp. 2303 ◽  
Author(s):  
Young-Je Kim ◽  
Un Ju Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Lipogenic Enzymes ◽  
Tissue Weight ◽  
Adipose Tissue Weight ◽  
Plasma Leptin ◽  
Type 2 Diabetic

This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db/db mice. Male C57BL/KsJ-db/db mice were fed a normal diet with or without HON (0.02%, w/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.

Edible Red Seaweed Campylaephora Hypnaeoides J. Agardh Alleviates Obesity and Related Metabolic Disorders in Mice by Suppressing Oxidative Stress and Inflammatory Response

2021 ◽  
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 ◽  
Public Health Problem ◽  
Serum Levels ◽  
Diet Group ◽  
Raw264.7 Cells ◽  
Edible Seaweed

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, diabetes, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor a (TNF-a), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-a, and interleukin-6 (IL-6) levels, while it decreased glutathione (GSH) and superoxide dismutase (SOD). 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-a in macrophage RAW264.7 cells. Conclusions: The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, diabetes, 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.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice

2008 ◽  
Vol 295 (2) ◽  
pp. E331-E338 ◽  
Author(s):  
Neel S. Singhal ◽  
Rajesh T. Patel ◽  
Yong Qi ◽  
Yun-Sik Lee ◽  
Rexford S. Ahima
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Wild Type ◽  
The Metabolic Syndrome ◽  
Expression Of Genes ◽  
Similar Body ◽  
Deficient Mice

Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice.

scholarly journals THE ROLE OF MYOKINES INTERSTITIAL INTERACTION AND REGULATION OF METABOLISM: A REVIEW OF LITERATURE

2016 ◽  
Vol 19 (1) ◽  
pp. 28-34
Author(s):  
T T Tsoriev ◽  
Zh E White ◽  
L Ya Rozhinskaya
Keyword(s):  
Skeletal Muscles ◽  
Metabolic Disorders ◽  
Visceral Obesity ◽  
Signal Pathways ◽  
Review Of Literature ◽  
Glucose And Lipid Metabolism ◽  
Regulation Of Metabolism ◽  
Skin Mucosa

Myokines are hormone-like acting molecules produced in skeletal muscles during and immediately after exercise. They affect both paracrine (inside the muscles themselves) and endocrine manner (in adipose tissue, liver, endothelium, skin, mucosa etc.) implementing different effects on target tissues, mainly through regulation of metabolic processes (such as glucose and lipid metabolism, growth and division of neurons and endothelial cells and others). The examination of myokines is of great interest for researchers of different medicine departments, particularly for endocrinologists, because of myokines’ involvement in pathogenesis of abdominal and visceral obesity, diabetes mellitus type 2 and cardiovascular diseases that are all the components of metabolic syndrome. The most important issue for clinicians is a possibility of future therapeutic implication of the myokine’s signal pathways in treatment of widespread metabolic disorders.

scholarly journals Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors

2021 ◽  
Vol 23 (1) ◽  
pp. 322
Author(s):  
Maria N. Evseeva ◽  
Maria S. Balashova ◽  
Konstantin Y. Kulebyakin ◽  
Yury P. Rubtsov
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Metabolic Disorders ◽  
Adipogenic Differentiation ◽  
In Vivo Studies ◽  
Research Review ◽  
Treatment And Prevention

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

scholarly journals Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katherine A Smith ◽  
Stephan Löser ◽  
Fumi Varyani ◽  
Yvonne Harcus ◽  
Henry J McSorley ◽  
...  
Keyword(s):  
Chronic Infection ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Wild Type ◽  
Heligmosomoides Polygyrus ◽  
Innate Effector ◽  
Interleukin 25 ◽  
Deficient Mice

Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and amplifying the type immune response to helminth parasites. However, its role in the later effector phase of clearing chronic infection remains unclear. The helminth Heligmosomoides polygyrus establishes long-term infections in susceptible C57BL/6 mice, but is slowly expelled in BALB/c mice from day 14 onwards. We noted that IL-25R (Il17rb)-deficient BALB/c mice were unable to expel parasites despite type 2 immune activation comparable to the wild-type. We then established that in C57BL/6 mice, IL-25 adminstered late in infection (days 14–17) drove immunity. Moreover, when IL-25 and IL-4 were delivered to Rag1-deficient mice, the combination resulted in near complete expulsion of the parasite, even following administration of an anti-CD90 antibody to deplete innate lymphoid cells (ILCs). Hence, effective anti-helminth immunity during chronic infection requires an innate effector cell population that is synergistically activated by the combination of IL-4Rα and IL-25R signaling.

scholarly journals Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation

2019 ◽  
Vol 20 (7) ◽  
pp. 1660 ◽  
Author(s):  
Alicia Bort ◽  
Belén Sánchez ◽  
Pedro Mateos-Gómez ◽  
Inés Díaz-Laviada ◽  
Nieves Rodríguez-Henche
Keyword(s):  
Hepg2 Cells ◽  
Metabolic Disorders ◽  
Dietary Habits ◽  
Neutral Lipids ◽  
Hepatic Lipogenesis ◽  
Diet Induced Obesity ◽  
Primary Health ◽  
Neutral Lipid Content ◽  
Chili Peppers

Obesity, a major risk factor for chronic diseases such as type 2 diabetes (T2D), represents a serious primary health problem worldwide. Dietary habits are of special interest to prevent and counteract the obesity and its associated metabolic disorders, including lipid steatosis. Capsaicin, a pungent compound of chili peppers, has been found to ameliorate diet-induced obesity in rodents and humans. The purpose of this study was to examine the effect of capsaicin on hepatic lipogenesis and to delineate the underlying signaling pathways involved, using HepG2 cells as an experimental model. Cellular neutral lipids, stained with BODIPY493/503, were quantified by flow cytometry, and the protein expression and activity were determined by immunoblotting. Capsaicin reduced basal neutral lipid content in HepG2 cells, as well that induced by troglitazone or by oleic acid. This effect of capsaicin was prevented by dorsomorphin and GW9662, pharmacological inhibitors of AMPK and PPARγ, respectively. In addition, capsaicin activated AMPK and inhibited the AKT/mTOR pathway, major regulators of hepatic lipogenesis. Furthermore, capsaicin blocked autophagy and increased PGC-1α protein. These results suggest that capsaicin behaves as an anti-lipogenic compound in HepG2 cells.

scholarly journals Potential Roles of Adipocyte Extracellular Vesicle–Derived miRNAs in Obesity-Mediated Insulin Resistance

2020 ◽  
Author(s):  
Yujeong Kim ◽  
Ok-Kyung Kim
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Extracellular Vesicle ◽  
Extracellular Mirnas

ABSTRACT Recently, extracellular microRNAs (miRNAs) from adipose tissue have been shown to be involved in the development of insulin resistance. Here, we summarize several mechanisms explaining the pathogenesis of obesity-induced insulin resistance and associated changes in the expression of obesity-associated extracellular miRNAs. We discuss how miRNAs, particularly miR-27a, miR-34a, miR-141-3p, miR-155, miR210, and miR-222, in extracellular vesicles secreted from the adipose tissue can affect the insulin signaling pathway in metabolic tissue. Understanding the role of these miRNAs will further support the development of therapeutics for obesity and metabolic disorders such as type 2 diabetes.

Dynamic Analysis of the Possible Effects of Leptin in Some Metabolic Disorders in Obesity

2012 ◽  
Vol 1 (4) ◽  
pp. 1-15
Author(s):  
Alejandro Talaminos ◽  
Laura M. Roa Romero
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Internal State ◽  
Control Mechanisms ◽  
State Variables ◽  
External Energy ◽  
Internal State Variables ◽  
Dynamic View ◽  
Great Relevance

Obesity and metabolic syndrome represent an increasing epidemiological challenge for society given the associated social and health implications. Obesity is related to different metabolic disorders, like diabetes mellitus type 2, which has been subject to study in the last decades. Nowadays, most of the related research focuses on endocrine aspects, especially related to adipose tissue. This is due to the fact that some adipocytokines are proven to be of great relevance as therapeutic agents both for obesity and mellitus type 2 diabetes. This work integrates some aspects of the knowledge generated under these research studies. In this context, it is proposed the design and development of a computational model that provides a better dynamic view of the existing interactions between endocrine aspects of the adipose tissue and glucose control mechanisms in people with obesity. The model behaves as an observer that estimates the dynamics of internal state variables, not easy to be measured in the clinical practice, and which helps to understand the dynamic behaviour of measurable variables. The work analyses the effects of the external energy intake and exercises over the obesity control and glycemia. The model has been validated by using other authors’ data. Predictions of the influence over the measurable variables of the behaviours considered when the virtual patient follows different diets and physical exercise are shown as results.

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