scholarly journals Estrogens Prevent Metabolic Dysfunctions Induced by Circadian Disruptions in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 2114-2123 ◽  
Author(s):  
Liangru Zhu ◽  
Fang Zou ◽  
Yongjie Yang ◽  
Pingwen Xu ◽  
Kenji Saito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Fat ◽  
Dependent Manner ◽  
Jet Lag ◽  
Altered Expression ◽  
Circadian Genes ◽  
Female Mice ◽  
Visceral Fat Accumulation ◽  
Metabolic Dysfunctions

Abstract Circadian disruption has become a significant factor contributing to the epidemics of obesity and insulin resistance. However, interventions to treat metabolic dysfunctions induced by circadian disruptions are limited. The ovarian hormone, estrogen, produces important antiobesity and antidiabetic effects in female animals and has profound effects on daily behavioral rhythms. Here, we show that in female mice depleted with endogenous estrogens, a jet-lag paradigm induced visceral fat accumulation and systemic insulin resistance, which were associated with altered expression of multiple circadian genes in the visceral fat depot. Interestingly, all these jet-lag-induced deficits were completely rescued in female mice supplemented with exogenous estrogens. We further examined 24-hour oscillations of circadian genes in adipose tissues in female mice with estrogen depletion or replacement and showed that expression levels of the circadian gene, period circadian protein homolog 2, oscillate in visceral adipose tissue in an estrogen-dependent manner. Together, our results indicate that estrogens interact with the intrinsic circadian clock in adipose tissue and prevent abnormal lipid accumulation caused by circadian disruptions.

scholarly journals Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

2013 ◽  
Vol 304 (12) ◽  
pp. E1321-E1330 ◽  
Author(s):  
Kazunari Nohara ◽  
Rizwana S. Waraich ◽  
Suhuan Liu ◽  
Mathieu Ferron ◽  
Aurélie Waget ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Adult Female ◽  
Sympathetic Tone ◽  
Visceral Adiposity ◽  
Androgen Excess ◽  
Altered Expression ◽  
Female Mice ◽  
The Impact

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

scholarly journals Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

2019 ◽  
Vol 3 (7) ◽  
pp. 1409-1416 ◽  
Author(s):  
Satoshi Kadowaki ◽  
Yoshifumi Tamura ◽  
Yuki Someya ◽  
Kageumi Takeno ◽  
Hideyoshi Kaga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Visceral Fat ◽  
Visceral Fat Area ◽  
Japanese Men ◽  
Fat Accumulation ◽  
Visceral Fat Accumulation ◽  
Intrahepatic Lipid

Abstract Context Asians have a high prevalence of insulin resistance, even in the nonobese state. Whereas both visceral fat accumulation (VFA) and fatty liver (FL) have been shown to be associated with insulin resistance, it is still unclear which is a better marker to predict insulin resistance in nonobese Asians. Objective The aim of this study was to investigate the relation between VFA or FL and insulin resistance in nondiabetic nonobese Japanese men who do not have diabetes. Design and Participants We studied 87 nonobese (body mass index <25 kg/m2) Japanese men without diabetes. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity in adipose tissue, muscle, and liver. Intrahepatic lipid and abdominal visceral fat area were measured by 1H-magnetic resonance spectroscopy and MRI, respectively. Subjects were divided into four groups based on the presence or absence of VFA (visceral fat area ≥100 cm2) and FL (intrahepatic lipid ≥ 5%): control (non-VFA, non-FL; n = 54), VFA only (n = 18), FL only (n = 7), and VFA plus FL (n = 8). Results Subjects in the FL only and VFA plus FL groups had insulin resistance in adipose tissue and muscle, as well as relatively lower hepatic insulin sensitivity. The specific insulin sensitivities in these organs were comparable in the VFA only and control groups. Conclusions In nonobese Japanese men without diabetes, subjects with FL only or VFA plus FL but not VFA only had insulin resistance, suggesting that FL may be a more useful clinical marker than VFA to predict insulin resistance in nonobese Japanese men without diabetes.

scholarly journals Sex Difference in Corticosterone-Induced Insulin Resistance in Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2367-2387 ◽  
Author(s):  
Kasiphak Kaikaew ◽  
Jacobie Steenbergen ◽  
Theo H van Dijk ◽  
Aldo Grefhorst ◽  
Jenny A Visser
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Prolonged Exposure ◽  
Morphological Changes ◽  
Elevated Serum ◽  
High Dose ◽  
Dependent Manner ◽  
Male Mice ◽  
Adipose Tissues ◽  
Female Mice

Abstract Prolonged exposure to glucocorticoids (GCs) causes various metabolic derangements. These include obesity and insulin resistance, as inhibiting glucose utilization in adipose tissues is a major function of GCs. Although adipose tissue distribution and glucose homeostasis are sex-dependently regulated, it has not been evaluated whether GCs affect glucose metabolism and adipose tissue functions in a sex-dependent manner. In this study, high-dose corticosterone (rodent GC) treatment in C57BL/6J mice resulted in nonfasting hyperglycemia in male mice only, whereas both sexes displayed hyperinsulinemia with normal fasting glucose levels, indicative of insulin resistance. Metabolic testing using stable isotope-labeled glucose techniques revealed a sex-specific corticosterone-driven glucose intolerance. Corticosterone treatment increased adipose tissue mass in both sexes, which was reflected by elevated serum leptin levels. However, female mice showed more metabolically protective adaptations of adipose tissues than did male mice, demonstrated by higher serum total and high-molecular-weight adiponectin levels, more hyperplastic morphological changes, and a stronger increase in mRNA expression of adipogenic differentiation markers. Subsequently, in vitro studies in 3T3-L1 (white) and T37i (brown) adipocytes suggest that the increased leptin and adiponectin levels were mainly driven by the elevated insulin levels. In summary, this study demonstrates that GC-induced insulin resistance is more severe in male mice than in female mice, which can be partially explained by a sex-dependent adaptation of adipose tissues.

Fatty Liver Is a Better Marker of Muscle Insulin Resistance than Visceral Fat Accumulation in Nonobese Japanese Men

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1854-P
Author(s):  
SATOSHI KADOWAKI ◽  
YOSHIFUMI TAMURA ◽  
YUKI SOMEYA ◽  
KAGEUMI TAKENO ◽  
TAKASHI FUNAYAMA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Visceral Fat ◽  
Japanese Men ◽  
Muscle Insulin Resistance ◽  
Fat Accumulation ◽  
Visceral Fat Accumulation

TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

2013 ◽  
Vol 305 (1) ◽  
pp. E101-E112 ◽  
Author(s):  
Ana Vázquez-Carballo ◽  
Victòria Ceperuelo-Mallafré ◽  
Matilde R. Chacón ◽  
Elsa Maymó-Masip ◽  
Margarita Lorenzo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Signaling ◽  
Visceral Fat ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Metabolic Effects ◽  
Human Adipocytes ◽  
Fat Depots ◽  
Tnf Α

Visceral fat is strongly associated with insulin resistance. Obesity-associated adipose tissue inflammation and inflammatory cytokine production are considered key mediators of insulin signaling inhibition. TWEAK is a relatively new member of the TNF cytokine superfamily, which can exist as full length membrane-associated (mTWEAK) and soluble (sTWEAK) isoforms. Although TWEAK has been shown to have important functions in chronic inflammatory diseases its physiological role in adipose tissue remains unresolved. In this study, we explore the molecular mechanisms involved in the modulation of TNF-α-induced effects on insulin sensitivity by sTWEAK in a human visceral adipose cell line and also in primary human adipocytes obtained from visceral fat depots. Our data reveal that sTWEAK ameliorates TNF-α-induced insulin resistance on glucose uptake, GLUT4 translocation and insulin signaling without affecting other metabolic effects of TNF-α such as lipolysis or apoptotis. Co-immunoprecipitation experiments in adipose cells revealed that pretreatment with sTWEAK specifically inhibits TRAF2 association with TNFR1, but not with TNFR2, which mediates insulin resistance. However, sTWEAK does not affect other downstream molecules activated by TNF-α, such as TAK1. Rather, sTWEAK abolishes the stimulatory effect of TNF-α on JNK1/2, which is directly involved in the development of insulin resistance. This is associated with an increase in PP2A activity upon sTWEAK treatment. Silencing of the PP2A catalytic subunit gene overcomes the dephosphorylation effect of sTWEAK on JNK1/2, pointing to PP2A as a relevant mediator of sTWEAK-induced JNK inactivation. Overall, our data reveal a protective role of TWEAK in glucose homeostasis and identify PP2A as a new driver in the modulation of TNF-α signaling by sTWEAK.

scholarly journals Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high-fat diet and ovariectomy in mice

2017 ◽  
Vol 312 (4) ◽  
pp. E300-E308 ◽  
Author(s):  
Kazuo Ohtake ◽  
Nobuyuki Ehara ◽  
Hiroshige Chiba ◽  
Genya Nakano ◽  
Kunihiro Sonoda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Visceral Fat ◽  
High Fat Diet ◽  
Hormone Replacement ◽  
Dependent Manner ◽  
High Fat ◽  
Alternative Source ◽  
Enos Activity

Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect on this syndrome. We examined the effect of dietary nitrite in a mouse model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) and a high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF with or without sodium nitrite (50 mg and 150 mg/l) in the drinking water. Daily food intake and weekly body weight were monitored for 18 wk. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and mice developed obesity with visceral hypertrophic adipocytes and increased transcriptional levels of monocyte chemoattractant protein-1, TNF-α, and IL-6 in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose-dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that an endogenous NO defect might underlie postmenopausal metabolic syndrome and that dietary nitrite provides an alternative source of NO, subsequently compensating for metabolic impairments of this syndrome.

scholarly journals Lower Birth Weight and Visceral Fat Accumulation Are Related to Hyperinsulinemia and Insulin Resistance in Obese Japanese Children

2005 ◽  
Vol 28 (6) ◽  
pp. 529-536 ◽  
Author(s):  
Yukie TANAKA ◽  
Toru KIKUCHI ◽  
Keisuke NAGASAKI ◽  
Makoto HIURA ◽  
Yohei OGAWA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Visceral Fat ◽  
Japanese Children ◽  
Fat Accumulation ◽  
Lower Birth Weight ◽  
Visceral Fat Accumulation

scholarly journals Hepatic inflammation precedes steatosis and is mediated by visceral fat accumulation

2020 ◽  
Vol 245 (3) ◽  
pp. 369-380 ◽  
Author(s):  
Breno Picin Casagrande ◽  
Daniel Vitor de Souza ◽  
Daniel Araki Ribeiro ◽  
Alessandra Medeiros ◽  
Luciana Pellegrini Pisani ◽  
...  
Keyword(s):  
Visceral Fat ◽  
Saturated Fatty Acids ◽  
Hdl Cholesterol ◽  
Dependent Manner ◽  
Hepatic Inflammation ◽  
Fat Accumulation ◽  
Visceral Fat Accumulation ◽  
Unhealthy Eating ◽  
Hepatic Fat ◽  
Simple Carbohydrates

The negative aspects of unhealthy eating on obesity and hepatic health are well described. The axis between the adipose tissue and the liver participates in most of the damage caused to this tissue regarding obesogenic diets (OD). At the same time that the effects of consuming simple carbohydrates and saturated fatty acids are known, the effects of the cessation of its intake are scarce. Withdrawing from OD is thought to improve health; despite some studies had shown improvement in hepatic conditions in the long-term, short-term studies were not found. Therefore, we aimed to determine how OD intake and withdrawal would influence visceral and hepatic fat accumulation and inflammation. To this end, male 60-days-old Wistar rats received standard chow (n = 16) or a high-sugar/high-fat diet (HSHF) for 30 days (n = 32), a cohort of the HSHF-fed animals was then kept 48 h on standard chow (n = 16). In opposition to the generally reported, the results indicate that hepatic inflammation preceded hepatic steatosis. Additionally, inflammatory markers on the liver positively correlated visceral adipokines and visceral fat accumulation mediated them in a deposit-dependent manner. At the same time, a 48-h withdrawal was capable of reverting most of the risen inflammatory mediators, although MyD88 and TNFα persisted and serum non-HDL cholesterol was higher than control levels.

scholarly journals Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance

2020 ◽  
Author(s):  
Vanessa Pellegrinelli ◽  
Segio Rodriguez-Cuenca ◽  
Christine Rouault ◽  
Hanna Schilbert ◽  
Sam Virtue ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Metabolic Dysfunction ◽  
Collagen Turnover ◽  
Metabolic Complications ◽  
Genetic Ablation ◽  
Metabolic Dysfunctions ◽  
Inflammatory Macrophages

Abstract Fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance that results from an impaired collagen turnover. Peptidase D (PEPD) plays a vital role in collagen turnover by degrading proline-containing dipeptides. Nevertheless, its specific function and importance in AT is unknown. GWAS identified the rs731839 variant in the locus near PEPD that uncouples obesity from insulin resistance and dyslipidaemia, thus indicating that defective PEPD might impair AT remodelling and exacerbate metabolic complications. Here we show that in human and murine obesity, PEPD expression and activity decrease in AT, coupled to the release of PEPD systemically. Both events, in turn, are associated with the accumulation of fibrosis in AT and insulin resistance. Using pharmacologic and genetic animal models of PEPD down-regulation, we show that whereas dysfunctional PEPD activity provokes AT fibrosis, it is the PEPD secreted by AT the main contributor to inflammation, insulin resistance and metabolic dysfunction. Also, PEPD originated in inflammatory macrophages (Mɸ), plays an essential role promoting fibro-inflammatory responses via activation of EGFR in Mɸ and preadipocytes. Using genetic ablation of pepd in Mɸ that prevents obesity-induced PEPD release, also averts AT fibro-inflammation and obesity-associated metabolic dysfunctions. Taking advantage of factor analysis, we have identified the coupling of prolidase decreased activity and increased systemic levels of PEPD as the essential pathogenic triggers of AT fibrosis and insulin resistance. Thus, PEPD produced by Mɸ qualifies as a biomarker of AT fibro-inflammation and a therapeutic target for AT fibrosis and obesity-associated insulin resistance and type 2 diabetes.

Sign in / Sign up

Export Citation Format

Share Document