scholarly journals Estrogen Impairs Adipose Tissue Expansion and Cardiometabolic Profile in Obese-Diabetic Female Rats

2021 ◽  
Vol 22 (24) ◽  
pp. 13573
Author(s):  
Melanie Raquel Martínez-Cignoni ◽  
Agustí González-Vicens ◽  
Andrea Morán-Costoya ◽  
Ana María Proenza ◽  
Magdalena Gianotti ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hormone Replacement ◽  
Tissue Expansion ◽  
Female Rats ◽  
Diabetic Rat ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Obesity And Diabetes ◽  
Zucker Diabetic Fatty Rats ◽  
Expansion Pattern

It has been reported that 17β-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue–heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women.

scholarly journals In Vivo Knockdown of Adipocyte Erythropoietin Receptor Does Not Alter Glucose or Energy Homeostasis

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3652-3659 ◽  
Author(s):  
Cynthia T. Luk ◽  
Sally Yu Shi ◽  
Diana Choi ◽  
Erica P. Cai ◽  
Stephanie A. Schroer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Physiological Role ◽  
Tissue Expansion ◽  
Erythropoietin Receptor ◽  
Tissue Specific ◽  
Epo Receptor ◽  
Beneficial Effects ◽  
Obesity And Diabetes

The growing prevalence of obesity and diabetes necessitate a better understanding of the role of adipocyte biology in metabolism. Increasingly, erythropoietin (EPO) has been shown to have extraerythropoietic and cytoprotective roles. Exogenous administration has recently been shown to have beneficial effects on obesity and diabetes in mouse models and EPO can modulate adipogenesis and insulin signaling in 3T3-L1 adipocytes. However, its physiological role in adipocytes has not been identified. Using male and female mice with adipose tissue-specific knockdown of the EPO receptor, we determine that adipocyte EPO signaling is not essential for the maintenance of energy homeostasis or glucose metabolism. Adipose tissue-specific disruption of EPO receptor did not alter adipose tissue expansion, adipocyte morphology, insulin resistance, inflammation, or angiogenesis in vivo. In contrast to the pharmacological effects of EPO, we demonstrate that EPO signaling at physiological levels is not essential for adipose tissue regulation of metabolism.

scholarly journals Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dependent Manner ◽  
Metabolic Dysfunction ◽  
Functional Interaction ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Adhesion Gpcr ◽  
Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

scholarly journals Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice

2019 ◽  
Vol 20 (6) ◽  
pp. 1462 ◽  
Author(s):  
Reem Atawia ◽  
Haroldo Toque ◽  
Mohamed Meghil ◽  
Tyler Benson ◽  
Nicole Yiew ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Normal Diet ◽  
Metabolic Dysfunction ◽  
Ppar Γ ◽  
Obesity And Diabetes ◽  
Visceral Adipose ◽  
Upregulated Genes

Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(−/−) or A1(+/−) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2−/−, but not A1+/−, mice. Additionally, A2−/− HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction.

scholarly journals Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

2013 ◽  
Vol 305 (3) ◽  
pp. E439-E450 ◽  
Author(s):  
Ping Kong ◽  
Carlos Gonzalez-Quesada ◽  
Na Li ◽  
Michele Cavalera ◽  
Dong-Wook Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Uptake ◽  
Cytokine Signaling ◽  
Vascular Density ◽  
Acid Uptake ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes.

scholarly journals Targeting Abdominal Obesity and Its Complications with Dietary Phytoestrogens

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 582 ◽  
Author(s):  
Alina Kuryłowicz ◽  
Marta Cąkała-Jakimowicz ◽  
Monika Puzianowska-Kuźnicka
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
Hormone Replacement ◽  
Visceral Obesity ◽  
Obese Individual ◽  
Dependent Manner ◽  
Metabolic Complications ◽  
Beneficial Effects ◽  
And Function

In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.

Oestrogen and stroke: the potential for harm as well as benefit

2006 ◽  
Vol 34 (6) ◽  
pp. 1362-1365 ◽  
Author(s):  
I.M. Macrae ◽  
H.V. Carswell
Keyword(s):  
Stroke Risk ◽  
Hormone Replacement ◽  
Epidemiological Studies ◽  
Artery Occlusion ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Stroke Incidence ◽  
Beneficial Effects ◽  
Ischaemic Brain

Epidemiological studies point to a beneficial influence of the female reproductive hormones on stroke risk in that women have a lower incidence of stroke prior to the menopause compared with men, but this difference weakens with age and stroke risk in women rises after the menopause. However, recent Women's Health Initiative trials in post-menopausal women report an increased stroke risk on hormone replacement therapy. An influence of gender is also apparent on stroke outcome in animal models: female rats exposed to transient MCA (middle cerebral artery) occlusion sustain less brain damage than age-matched males, with loss of protection following ovariectomy. The major hormone thought to be responsible for beneficial influences on stroke incidence and outcome is oestrogen, and a large preclinical literature now exists where exogenously administered oestrogen has been studied in male and ovariectomized female rats using a range of stroke models and outcome measures. Most of these studies administer oestrogen prior to the stroke, use a model of transient ischaemia followed by reperfusion and report a significant oestrogen-induced neuroprotection. However, in some studies where the MCA is permanently occluded, oestrogen pre-treatment in ovariectomized female rats has been shown to significantly exacerbate ischaemic damage. Therefore preclinical results demonstrate harmful as well as beneficial influences of oestrogen on the ischaemic brain, highlighting the need for further study to elucidate the mechanisms responsible for both detrimental and beneficial influences. Ultimately, this could lead to the development of new classes of oestrogenic compounds with improved risk/benefit profiles, designed to selectively activate pathways inducing only the beneficial effects of oestrogen in vivo.

scholarly journals D-allulose ameliorates adiposity through the AMPK-SIRT1-PGC-1α pathway in HFD-induced SD rats

2021 ◽  
Author(s):  
Geum Hwa Lee ◽  
Cheng Peng ◽  
Hwa-Young Lee ◽  
Seon-Ah Park ◽  
The-Hiep Hoang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Weight Gain ◽  
Chow Diet ◽  
Metabolic Dysfunction ◽  
Sprague Dawley ◽  
Metabolic Disturbances ◽  
Beneficial Effects ◽  
Reduced Body

Background: Adiposity is a major health-risk factor, and D-allulose has beneficial effects on adiposity-related metabolic disturbances. However, the modes of action underlying anti-hyperglycemic and hypolipidemic activity are partly understood. Objective: This study investigated the in vivo and in vitro effects of D-allulose involved in adipogenesis and activation of the AMPK/SIRT1/PGC-1α pathway in high-fat diet (HFD)-fed rats. Design: In this study, 8-week-old male SD (Sprague Dawley) rats were divided into five groups (n = 8/group), (1) Control (chow diet, 3.5%); (2) 60% HFD; (3) 60% HFD supplemented with allulose powder (AP) at 0.4 g/kg; (4) 60% HFD supplemented with allulose liquid (AL) at 0.4 g/kg; (5) 60% HFD supplemented with glucose (AL) at 0.4 g/kg. All the group received the product through oral gavage for 6 weeks. Control and HFD groups were gavaged with double-distilled water. Results: Rats receiving AP and AL showed reduced body weight gain and fat accumulation in HFD-fed rats. Also, supplementation of AL/AP regulated the cytokine secretion and recovered biochemical parameters to alleviate metabolic dysfunction and hepatic injury. Additionally, AL/AP administration improved adipocyte differentiation via regulation of the PPARγ and C/EBPα signaling pathway and adipogenesis-related genes owing to the combined effect of the AMPK/SIRT1 pathway. Furthermore, AL/AP treatment mediated PGC-1α expression triggering mitochondrial genesis via activating the AMPK phosphorylation and SIRT1 deacetylation activity in adipose tissue. Conclusion: The anti-adiposity activity of D-allulose is observed on a marked alleviation in adipogenesis and AMPK/SIRT1/PGC-1α deacetylation in the adipose tissue of HFD-fed rat.

scholarly journals Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Safaa H. Hammoud ◽  
Ibrahim AlZaim ◽  
Yusra Al-Dhaheri ◽  
Ali H. Eid ◽  
Ahmed F. El-Yazbi
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Tissue Expansion ◽  
Renal Diseases ◽  
Metabolic Dysfunction ◽  
Perirenal Adipose Tissue ◽  
Local Mechanism ◽  
Glucose And Lipid Homeostasis ◽  
The Impact

A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role. Adipose tissue was shown to synthesize and secrete adipokines that are pertinent to glucose and lipid homeostasis, as well as inflammation. Importantly, the obesity-induced adipose tissue expansion stimulates a plethora of signals capable of triggering an inflammatory response. These inflammatory manifestations of obese AT have been linked to insulin resistance, metabolic syndrome, and type 2 diabetes, and proposed to evoke obesity-induced comorbidities including cardiovascular diseases (CVDs). A growing body of evidence suggests that metabolic disorders, characterized by AT inflammation and accumulation around organs may eventually induce organ dysfunction through a direct local mechanism. Interestingly, perirenal adipose tissue (PRAT), surrounding the kidney, influences renal function and metabolism. In this regard, PRAT emerged as an independent risk factor for chronic kidney disease (CKD) and is even correlated with CVD. Here, we review the available evidence on the impact of PRAT alteration in different metabolic states on the renal and cardiovascular function. We present a broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT. We also argue that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.

CTRP6 rapidly responds to acute nutritional changes, regulating adipose tissue expansion and inflammation in mice

2021 ◽  
Author(s):  
Rotem Lahav ◽  
Yulia Haim ◽  
Nikhil Suresh Bhandarkar ◽  
Liron Levin ◽  
Vered Chalifa-Caspi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Tissue Expansion ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Wild Type ◽  
High Fat ◽  
Tnf Α ◽  
Fat Feeding ◽  
Nutritional Changes

In chronic obesity, activated adipose tissue pro-inflammatory cascades are tightly linked to metabolic dysfunction. Yet, close temporal analyses of the responses to obesogenic environment such as high-fat feeding (HFF) in susceptible mouse strains question the causal relationship between inflammation and metabolic dysfunction, and/or raises the possibility that certain inflammatory cascades play adaptive/homeostatic, rather than pathogenic roles. Here we hypothesized that CTRP6, a C1QTNF family member, may constitute an early responder to acute nutritional changes in adipose tissue, with potential physiological roles. Both 3 days high-fat feeding (3dHFF) and acute obesity reversal (2 weeks switch to low-fat diet after 8w-HFF) already induced marked changes in whole-body fuel utilization. While adipose tissue expression of classical pro-inflammatory cytokines (Tnf-α, Ccl2, Il1b) exhibited no, or only minor, change, C1qtnf6 uniquely increased, and decreased, in response to 3dHFF and acute obesity reversal, respectively. CTRP6 knockout (KO) mouse embryonic fibroblasts (MEF) exhibited increased adipogenic gene expression (Pparg, Fabp4, Adipoq) and markedly reduced inflammatory genes (Tnf-α, Ccl2, Il6) compared to wild-type MEF, and recombinant CTRP6 induced the opposite gene expression signature, as assessed by RNA-sequencing. Consistently, 3dHFF of CTRP6-KO mice induced a greater whole-body and adipose tissue weight gain compared to wild-type littermates. Collectively, we propose CTRP6 as a gene that rapidly responds to acute changes in caloric intake, acting in acute over-nutrition to induce a "physiological inflammatory response" that limits adipose tissue expansion.

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