scholarly journals Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haruka Kimura ◽  
Tomohisa Nagoshi ◽  
Yuhei Oi ◽  
Akira Yoshii ◽  
Yoshiro Tanaka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Cold Exposure ◽  
Lipid Droplets ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Ucp1 Expression ◽  
Tissue Browning

AbstractIncreasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.

scholarly journals Treatment With Atrial Natriuretic Peptide Induces Adipose Tissue Browning and Exerts Thermogenic Actions in Vivo.

2021 ◽  
Author(s):  
Haruka Kimura ◽  
Tomohisa Nagoshi ◽  
Yuhei Oi ◽  
Akira Yoshii ◽  
Yoshiro Tanaka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Cold Exposure ◽  
Lipid Droplets ◽  
Tolerance Test ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Tissue Browning

Abstract Background: Although natriuretic peptides (NPs) classically act on the renal and cardiovascular systems, increasing evidence suggests that NPs also largely coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported that A-type NP (ANP) raises the intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether or not exogenous ANP treatment exerts a significant impact on adipose tissues in vivo using diet-induced obese mice.Methods and Results: C57BL/6 mice fed a high-fat diet (HFD) or normal-fat diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously via osmotic pump for another 3 weeks (0.5 μg/kg/min). The intraperitoneal glucose tolerance test and insulin tolerance test showed that ANP treatment significantly ameliorated HFD-induced insulin resistance. Histological analyses revealed that HFD increased the brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT (eWAT), and hepatic steatosis, all of which were substantially attenuated by ANP treatment. Likewise, ANP treatment markedly increased the expression of uncoupling protein-1 (UCP1), a specific marker of BAT, in iWAT (browning). ANP also further increased the UCP1 expression in BAT with an NFD. Accordingly, the cold tolerance test (at 4 °C for 4 h) demonstrated that the ANP-treated mice were tolerant to cold exposure.Conclusions: Exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis as well as by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.

Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis

2008 ◽  
Vol 294 (4) ◽  
pp. E688-E697 ◽  
Author(s):  
G. Medina-Gomez ◽  
R. M. Calvo ◽  
M.-J. Obregon
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Thyroid Stimulating Hormone ◽  
Low Doses ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Thyroid Axis ◽  
Rat Adipose Tissue

Triiodothyroacetic acid (TRIAC) is a physiological product of triiodothyronine (T3) metabolism, with high affinity for T3 nuclear receptors. Its interest stems from its potential thermogenic effects. Thus this work aimed 1) to clarify these thermogenic effects mediated by TRIAC vs. T3 in vivo and 2) to determine whether they occurred predominantly in adipose tissues. To examine this, control rats were infused with equimolar T3 or TRIAC doses (0.8 or 4 nmol·100 g body wt−1·day−1) or exposed for 48 h to cold. Both T3 doses and only the highest TRIAC dose inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T4) in plasma and tissues. Interestingly, the lower TRIAC dose marginally inhibited plasma T4. T3 infusion increased plasma and tissue T3 in a tissue-specific manner. The highest TRIAC dose increased TRIAC concentrations in plasma and tissues, decreasing plasma T3. TRIAC concentrations in tissues were <10% those of T3. Under cold exposure or high T3 doses, TRIAC increased only in white adipose tissue (WAT). Remarkably, only the lower TRIAC dose activated thermogenesis, inducing ectopic uncoupling protein (UCP)-1 expression in WAT and maximal increases in UCP-1, UCP-2, and lipoprotein lipase (LPL) expression in brown adipose tissue (BAT), inhibiting UCP-2 in muscle and LPL in WAT. TRIAC, T3, and cold exposure inhibited leptin secretion and mRNA in WAT. In summary, TRIAC, at low doses, induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia, suggesting a specific role regulating energy balance. This selective effect of TRIAC in adipose tissues might be considered a potential tool to increase energy metabolism.

Fatty acid synthesis in adipose tissues of physically trained rats in vivo

1983 ◽  
Vol 245 (1) ◽  
pp. E8-E13
Author(s):  
K. Tokuyama ◽  
H. Okuda
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Physical Training ◽  
Dark Period ◽  
Acid Synthesis ◽  
Free Access ◽  
Adipose Tissues ◽  
Brown Adipose

The effect of physical training on fatty acid synthesis in vivo was studied. After the rats had free access to a running wheel for 50 days, the rate of fatty acid synthesis estimated using 3H2O in adipose tissues of trained rats was about three times higher than that of sedentary rats in both the light and dark period. The rate of fatty acid synthesis in the liver but not in the brown adipose tissue was also slightly enhanced by physical training. The number of adipocytes was not affected, but the size of adipocytes was reduced by physical training. In trained rats, the rate of fatty acid synthesis in adipocytes whose diameter was similar to that of sedentary rats was about 10 times higher than that of sedentary rats. Within adipose tissue, the rate of fatty acid synthesis correlated positively to the diameter of adipocytes both in the sedentary and trained rats. These findings mean that the adaptive increase in fatty acid synthesis seen in adipocytes of trained rats is not secondary to the reduction in size of adipocytes.

The development of insulin resistance in brown adipose tissue may impair the acute cold-induced activation of thermogenesis in genetically obese (ob/ob) mice

1984 ◽  
Vol 4 (11) ◽  
pp. 933-940 ◽  
Author(s):  
Stewart W. Mercer ◽  
Paul Trayhurn
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Brown Fat ◽  
Acute Cold Exposure ◽  
Brown Adipose

Genetically obese (ob/ob) mice develop insulin resistance in brown adipose tissue during the fifth week of life. Prior to this, at 26 days of age, oh/oh mice show a substantial increase in GDP binding to brownadipose-tissue mitochondria during acute cold exposure. When insulin resistance in brown fat develops, by 35 days of age, the increase in GDP binding in response to cold is markedly reduced. Studies with 2-deoxyglucose suggest that insulin resistance in brown adipose tissue could impair thermogenic responsiveness during acute cold exposure by limiting the ability of the tissue to take up glucose.

Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats

1986 ◽  
Vol 251 (5) ◽  
pp. E576-E583 ◽  
Author(s):  
L. H. Storlien ◽  
D. E. James ◽  
K. M. Burleigh ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Brown Adipose ◽  
Glucose Output ◽  
Fat Feeding

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals URAT1-selective inhibition ameliorates insulin resistance by attenuating diet-induced hepatic steatosis and BAT whitening in mice

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Tanaka ◽  
T Nagoshi ◽  
A Yoshii ◽  
Y Oi ◽  
H Takahashi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Critical Role ◽  
Selective Inhibition ◽  
Selective Inhibitor ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Brown Adipose

Abstract Background Accumulating evidence suggests that high uric acid is strongly associated with obesity and metabolic syndrome and drives the development of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Although urate transporter-1 (URAT1), which is primarily expressed in the kidney, plays a critical role in the development of hyperuricemia, its pathophysiological implication in NAFLD and insulin resistance remains unclear. Objectives We hypothesizes that URAT1 plays an important role in obesity-induced metabolic disorders, and URAT1-selective inhibitor treatment ameliorates systemic insulin resistance, NAFLD and adipose tissue dysfunction using diet-induced obese mice. Methods Mice fed a high-fat diet (HFD) for 16 to 18 weeks or a normal-fat diet (NFD) were treated with or without a novel oral URAT1-selective inhibitor (dotinurad [50 mg/kg/day]) for another 4 weeks. Results Dotinurad administration significantly ameliorated HFD-induced obesity and insulin resistance. We found that URAT1 was also expressed in the liver and brown adipose tissue (BAT) other than kidney. HFD markedly induced NAFLD, which was characterized by severe hepatic steatosis, as well as the elevation of serum ALT activity and tissue inflammatory cytokine genes (Ccl2 and TNFα), all of which were attenuated by dotinurad. Likewise, HFD significantly increased URAT1 expression in BAT, resulting in the lipid accumulation (whitening of BAT) and increased production of tissue reactive oxygen species, which were reduced by dotinurad via UCP1 activation. Conclusions A novel URAT1-selective inhibitor, dotinurad, ameliorates insulin resistance by attenuating hepatic steatosis and promoting rebrowning of lipid-rich BAT in HFD-induced obese mice. URAT1 serves as a key regulator of the pathophysiology of metabolic syndrome, and may be a new therapeutic target for insulin-resistant individuals, particularly those with concomitant NAFLD. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Median preoptic area neurons are required for the cooling and febrile activations of brown adipose tissue thermogenesis in rat

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ellen Paula Santos da Conceição ◽  
Shaun F. Morrison ◽  
Georgina Cano ◽  
Pierfrancesco Chiavetta ◽  
Domenico Tupone
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Preoptic Area ◽  
Therapeutic Approaches ◽  
Dorsomedial Hypothalamus ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

Abstract Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level of activation of brown adipose tissue (BAT) thermogenesis. We employed neuroanatomical and in vivo electrophysiological techniques to identify a source of excitation to thermogenesis-promoting neurons in the DMH that is required for cold defense and fever. Inhibition of median preoptic area (MnPO) neurons blocked the BAT thermogenic responses during both PGE2-induced fever and cold exposure. Disinhibition or direct activation of MnPO neurons induced a BAT thermogenic response in warm rats. Blockade of ionotropic glutamate receptors in the DMH, or brain transection rostral to DMH, blocked cold-evoked or NMDA in MnPO-evoked BAT thermogenesis. RNAscope technique identified a glutamatergic population of MnPO neurons that projects to the DMH and expresses c-Fos following cold exposure. These discoveries relative to the glutamatergic drive to BAT sympathoexcitatory neurons in DMH augment our understanding of the central thermoregulatory circuitry in non-torpid mammals. Our data will contribute to the development of novel therapeutic approaches to induce therapeutic hypothermia for treating drug-resistant fever, and for improving glucose and energy homeostasis.

Novel Aspects of White Adipose Tissue Browning by Thyroid Hormones

2019 ◽  
Vol 128 (06/07) ◽  
pp. 446-449 ◽  
Author(s):  
Kerstin Krause
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormones ◽  
White Adipose Tissue ◽  
Brown Adipocytes ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Tissue Browning ◽  
Thermogenic Capacity ◽  
Thermogenic Response

AbstractThyroid hormones are essential for the full thermogenic capacity of brown adipose tissue. The thermogenic response of brown adipocytes to thyroid hormones is resulting from the synergistic interaction of thyroid hormones with the sympathetic nervous system. In recent years, evidence has been provided that thyroid hormones also induce the browning of white adipose tissues. This review will provide a brief overview about the recent findings regarding the effects of thyroid hormones on adipose tissue thermogenesis including central and peripheral regulation of white adipose tissue browning.

scholarly journals Cold Exposure Differentially Stimulates Angiogenesis in BAT and WAT of Mice: Implication in Adrenergic Activation

2017 ◽  
Vol 42 (3) ◽  
pp. 974-986 ◽  
Author(s):  
Xiao Luo ◽  
Ru Jia ◽  
Xiao-qin Luo ◽  
Guan Wang ◽  
Qiang-ling Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cold Exposure ◽  
Angiogenic Factors ◽  
Adipose Tissues ◽  
Interscapular Brown Adipose Tissue ◽  
White Adipocytes ◽  
Adrenoceptor Agonist ◽  
Brown Adipose

Background/Aims: To characterize the temporal profile of cold-induced angiogenesis in brown and white adipose tissues of mice in vivo and the temporal changes of angiogenic factors in primary mice brown (BA) and white adipocytes (WA) treated with β3-adrenoceptor agonist (CL316,243) in vitro. Methods: 8-week old male C57BL/6J mice were individually housed in conventional cages under cold exposure (4°C) for 1, 2, 3, 4 and 5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissues (eWAT) were harvested for immunohistochemical and gene expression analysis. In vitro, primary mice BA and WA treated with or without CL316,243 were harvested for gene expression and protein secretion analysis. Results: A combination of morphological and genetic (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) analyses demonstrated depot-specific angiogenesis in response to cold exposure. Upon CL316,243 treatment, angiogenic factors (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) and secreted protein VEGFA were transiently increased in both BA and WA. Conclusion: Our results show that iBAT is highly responsive to cold-induced angiogenesis that is mainly supported by sWAT with a lesser extent by eWAT. Moreover, the angiogenesis is a transient process with the angiogenic factors may work in an autocrine/paracrine manner.

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