scholarly journals Antioxidant effects of N-acetylcysteine prevent programmed metabolic disease in mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Maureen J. Charron ◽  
Lyda Williams ◽  
Yoshinori Seki ◽  
Xiu Quan Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Disease ◽  
Adipose Tissue ◽  
Postnatal Growth ◽  
In Utero ◽  
Leptin Resistance ◽  
Maternal Weight ◽  
Insulin Tolerance ◽  
Brown Adipose ◽  
Increased Risk

An adverse maternal <i>in utero</i> environment can program offspring for increased risk for metabolic disease. The aim of this study was to determine whether N-acetylcysteine (NAC), an anti-inflammatory antioxidant, attenuates programmed susceptibility to obesity and insulin resistance in high fat diet (HFD) offspring. CD1 female mice were acutely fed a standard breeding chow or HFD. NAC was added to the drinking water (1g/kg) of the treatment cohorts from embryonic day 0.5 (e0.5) until the end of lactation. NAC treatment normalized HFD-induced maternal weight gain and oxidative stress, improved the maternal lipidome and prevented maternal leptin resistance. These favorable changes in the <i>in utero</i> environment normalized postnatal growth, decreased white adipose tissue (WAT) and hepatic fat, improved glucose and insulin tolerance and antioxidant capacity, reduced leptin and insulin and increased adiponectin in HFD offspring. The lifelong metabolic improvements in the offspring were accompanied by reductions in pro-inflammatory gene expression in liver and WAT and increased thermogenic gene expression in brown adipose tissue (BAT). These results, for the first time, provide a mechanistic rationale for how NAC can prevent the onset of metabolic disease in the offspring of mothers who consume a typical Western HFDs.

scholarly journals Antioxidant effects of N-acetylcysteine prevent programmed metabolic disease in mice

2020 ◽  
Author(s):  
Ada Admin ◽  
Maureen J. Charron ◽  
Lyda Williams ◽  
Yoshinori Seki ◽  
Xiu Quan Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Disease ◽  
Adipose Tissue ◽  
Postnatal Growth ◽  
In Utero ◽  
Leptin Resistance ◽  
Maternal Weight ◽  
Insulin Tolerance ◽  
Brown Adipose ◽  
Increased Risk

An adverse maternal <i>in utero</i> environment can program offspring for increased risk for metabolic disease. The aim of this study was to determine whether N-acetylcysteine (NAC), an anti-inflammatory antioxidant, attenuates programmed susceptibility to obesity and insulin resistance in high fat diet (HFD) offspring. CD1 female mice were acutely fed a standard breeding chow or HFD. NAC was added to the drinking water (1g/kg) of the treatment cohorts from embryonic day 0.5 (e0.5) until the end of lactation. NAC treatment normalized HFD-induced maternal weight gain and oxidative stress, improved the maternal lipidome and prevented maternal leptin resistance. These favorable changes in the <i>in utero</i> environment normalized postnatal growth, decreased white adipose tissue (WAT) and hepatic fat, improved glucose and insulin tolerance and antioxidant capacity, reduced leptin and insulin and increased adiponectin in HFD offspring. The lifelong metabolic improvements in the offspring were accompanied by reductions in pro-inflammatory gene expression in liver and WAT and increased thermogenic gene expression in brown adipose tissue (BAT). These results, for the first time, provide a mechanistic rationale for how NAC can prevent the onset of metabolic disease in the offspring of mothers who consume a typical Western HFDs.

scholarly journals Regulation of gene expression by FSP27 in white and brown adipose tissue

BMC Genomics ◽  
2010 ◽  
Vol 11 (1) ◽  
pp. 446 ◽  
Author(s):  
De Li ◽  
Yinxin Zhang ◽  
Li Xu ◽  
Linkang Zhou ◽  
Yue Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Regulation Of Gene Expression ◽  
Brown Adipose

scholarly journals Adipocyte-specific deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality

2021 ◽  
Author(s):  
Mario Gomez Salazar ◽  
Iris Pruñonosa Cervera ◽  
Rongling Wang ◽  
Karen French ◽  
Ruben García-Martín ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Energy Expenditure ◽  
Therapeutic Strategy ◽  
Oxygen Sensor ◽  
Modern Human ◽  
Protein Levels ◽  
Serum Proteomics ◽  
Potential Biomarker ◽  
Brown Adipose ◽  
Increased Risk

AbstractEnhancing brown adipose tissue (BAT) function to combat metabolic disease is a promising therapeutic strategy. A major obstacle to this strategy is that a thermoneutral environment, relevant to most modern human living conditions, deactivates functional BAT. We showed that we can overcome the dormancy of BAT at thermoneutrality by inhibiting the main oxygen sensor HIF-prolyl hydroxylase, PHD2, specifically in adipocytes. Mice lacking adipocyte PHD2 (P2KOad) and housed at thermoneutrality maintained greater BAT mass, had detectable UCP1 protein expression in BAT and higher energy expenditure. Mouse brown adipocytes treated with the pan-PHD inhibitor, FG2216, exhibited higher Ucp1 mRNA and protein levels, effects that were abolished by antagonising the canonical PHD2 substrate, HIF-2a. Induction of UCP1 mRNA expression by FG2216, was also confirmed in human adipocytes isolated from obese individuals. Human serum proteomics analysis of 5457 participants in the deeply phenotyped Age, Gene and Environment Study revealed that serum PHD2 (aka EGLN1) associates with increased risk of metabolic disease. Our data suggest adipose–selective PHD2 inhibition as a novel therapeutic strategy for metabolic disease and identify serum PHD2 as a potential biomarker.

Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue

1997 ◽  
Vol 273 (2) ◽  
pp. R762-R767 ◽  
Author(s):  
A. Chaudhry ◽  
J. G. Granneman
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adenylyl Cyclase ◽  
Regulation Of Gene Expression ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Functional Responses ◽  
Synergistic Interactions ◽  
Brown Adipose

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.

Opposite Effects of Voluntary Physical Exercise on β3-Adrenergic Receptors in the White and Brown Adipose Tissue

2019 ◽  
Vol 51 (09) ◽  
pp. 608-617 ◽  
Author(s):  
Lucia Balagova ◽  
Jan Graban ◽  
Agnesa Puhova ◽  
Daniela Jezova
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Uncoupling Protein ◽  
Control Diet ◽  
Tryptophan Depletion ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Exercise Induced

AbstractCatecholamine effects via β3-adrenergic receptors are important for the metabolism of the adipose tissue. Physical exercise is a core component of antiobesity regimens. We have tested the hypothesis that voluntary wheel running results in enhancement of β3-adrenergic receptor gene expression in the white and brown adipose tissues. The secondary hypothesis is that dietary tryptophan depletion modifies metabolic effects of exercise. Male Sprague-Dawley rats were assigned for sedentary and exercise groups with free access to running wheels for 3 weeks. All animals received normal control diet for 7 days. Both groups were fed either by low tryptophan (0.04%) diet or by control diet (0.2%) for next 2 weeks. The β3-adrenergic receptor mRNA levels in response to running increased in the retroperitoneal and epididymal fat pads. The gene expression of uncoupling protein-1 (UCP-1) was increased in the brown, while unchanged in the white fat tissues. Unlike control animals, the rats fed by low tryptophan diet did not exhibit a reduction of the white adipose tissue mass. Tryptophan depletion resulted in enhanced concentrations of plasma aldosterone and corticosterone, but had no influence on exercise-induced adrenal hypertrophy. No changes in β3-adrenergic receptor and cell proliferation measured by 5-bromo-2′-deoxyuridine incorporation in left heart ventricle were observed. The reduced β3-adrenergic receptor but not enhanced uncoupling protein-1 gene expression supports the hypothesis on hypoactive brown adipose tissue during exercise. Reduction in dietary tryptophan had no major influence on the exercise-induced changes in the metabolic parameters measured.

scholarly journals Pharmacological Inhibition of Soluble Epoxide Hydrolase by t-TUCB Improves Brown Adipose Tissue Activities in Diet-Induced Obesity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1703-1703
Author(s):  
Yang Yang ◽  
Xinyun Xu ◽  
Katie Graham ◽  
Ahmed Bettaieb ◽  
Christophe Morisseau ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Obese Mice ◽  
Treatment And Prevention ◽  
Insulin Tolerance ◽  
Brown Adipose

Abstract Objectives Brown adipose tissue (BAT), responsible for energy expenditure through nonshivering thermogenesis, has emerged as a novel target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH), encoded by Ephx2 gene, is a cytosolic enzyme that converts epoxy fatty acids (EpFAs) that are produced by cytochrome P-450 enzymes from polyunsaturated fatty acids into less active diols. Pharmacological inhibitors of sEH, such as trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB), have been shown to be beneficial for chronic diseases by inhibiting the degradation of EpFAs. We have previously shown that t-TUCB dose-dependently promotes brown adipogenesis in vitro. This study investigated the therapeutic effects of t-TUCB on BAT activation in diet-induced obese mice. Methods Male C57BL6/J mice were fed a high-fat diet (60% kcal from fat) for 8 weeks followed by random assignment into either the control or t-TUCB group (n = 10 per group) to receive either the vehicle control or t-TUCB (3 mg/kg/day) via osmotic minipump delivery at the subcutaneous area near the interscapular BAT for 6 weeks. Bodyweight and food intake, glucose and insulin tolerance tests, cold tolerance tests, and indirect calorimetry were measured before the mice were euthanized for further biochemical analysis. Results sEH inhibition by t-TUCB in the obese mice did not change body weight, fat pad weight, food intake, fasting blood glucose, glucose and insulin tolerance, or cold tolerance, but significantly decreased blood triglyceride levels and increased heat production during both day and night. Moreover, t-TUCB significantly increased protein expression of brown marker gene PGC-1alpha and lipid droplet-associated protein perilipin (PLIN), but not uncoupling protein 1 (UCP1), in the interscapular BAT of diet-induced obese mice. Conclusions Our results suggest that sEH pharmacological inhibition may be beneficial for BAT activation by increasing mitochondrial biogenesis and lipolysis in the BAT. Further studies using the sEH inhibitors and/or EpFA generating diets for obesity treatment and prevention are warranted. Funding Sources The work was supported by NIH 1R15DK114790–01A1 (to L.Z.), K99DK100736 and R00DK100736 (to A.B.), R15AT008733 (to S.W.), R35 ES030443 and P42ES004699 (to B.D.H).

Sign in / Sign up

Export Citation Format

Share Document