Tissue-specific effect of refeeding after short- and long-term caloric restriction on malic enzyme gene expression in rat tissues.

Restricting food intake to a level below that consumed voluntarily (85%, 70% and 50% of the ad libitum energy intake for 3 or 30 days) and re-feeding ad libitum for 48 h results in an increase of malic enzyme (ME) gene expression in rat white adipose tissue. The increase of ME gene expression was much more pronounced in rats maintained on restricted diet for 30 days than for 3 days. The changes in ME gene expression resembled the changes in the content of SREBP-1 in white adipose tissue. A similar increase of serum insulin concentration was observed in all groups at different degrees of caloric restriction and refed ad libitum for 48 h. Caloric restriction and refeeding caused on increase of ME activity also in brown adipose tissue (BAT) and liver. However, in liver a significant increase of ME activity was found only in rats maintained on the restricted diet for 30 days. No significant changes after caloric restriction and refeeding were found in heart, skeletal muscle, kidney cortex, and brain. These data indicate that the increase of ME gene expression after caloric restriction/refeeding occurs only in lipogenic tissues. Thus, one can conclude that caloric restriction/refeeding increases the enzymatic capacity for fatty acid biosynthesis.

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Caloric Restriction Paradoxically Increases Adiposity in Mice With Genetically Reduced Insulin

Endocrinology ◽

10.1210/en.2016-1102 ◽

2016 ◽

Vol 157 (7) ◽

pp. 2724-2734 ◽

Cited By ~ 11

Author(s):

Derek A. Dionne ◽

Søs Skovsø ◽

Nicole M. Templeman ◽

Susanne M. Clee ◽

James D. Johnson

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Caloric Restriction ◽

Gene Dosage ◽

Tissue Growth ◽

Tissue Mass ◽

Brown Adipose ◽

Paradoxical Effects ◽

Plasma Insulin Levels ◽

Ad Libitum

Antiadiposity effects of caloric restriction (CR) are associated with reduced insulin/IGF-1 signaling, but it is unclear whether the effects of CR would be additive to genetically reducing circulating insulin. To address this question, we examined female Ins1+/−:Ins2−/− mice and Ins1+/+:Ins2−/− littermate controls on either an ad libitum or 60% CR diet. Although Igf1 levels declined as expected, CR was unable to reduce plasma insulin levels in either genotype below their ad libitum-fed littermate controls. In fact, 53-week-old Ins1+/−:Ins2−/− mice exhibited a paradoxical increase in circulating insulin in the CR group compared with the ad libitum-fed Ins1+/−:Ins2−/− mice. Regardless of insulin gene dosage, CR mice had lower fasting glucose and improved glucose tolerance. Although body mass and lean mass predictably fell after CR initiation, we observed a significant and unexpected increase in fat mass in the CR Ins1+/−:Ins2−/− mice. Specifically, inguinal fat was significantly increased by CR at 66 weeks and 106 weeks. By 106 weeks, brown adipose tissue mass was also significantly increased by CR in both Ins1+/−:Ins2−/− and Ins1+/+:Ins2−/− mice. Interestingly, we observed a clear whitening of brown adipose tissue in the CR groups. Mice in the CR group had altered daily energy expenditure and respiratory exchange ratio circadian rhythms in both genotypes. Multiplexed analysis of circulating hormones revealed that CR was associated with increased fasting and fed levels of the obesogenic hormone, glucose-dependent insulinotropic polypeptide. Collectively these data demonstrate CR has paradoxical effects on adipose tissue growth in the context of genetically reduced insulin.

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Immunochemical studies with soluble and mitochondrial pyruvate carboxylase activities from rat tissues

Biochemical Journal ◽

10.1042/bj1190735 ◽

1970 ◽

Vol 119 (4) ◽

pp. 735-742 ◽

Cited By ~ 46

Author(s):

F. J. Ballard ◽

R. W. Hanson ◽

Lea Reshef

Keyword(s):

Adipose Tissue ◽

Mammary Gland ◽

Brown Adipose Tissue ◽

Rat Liver ◽

White Adipose Tissue ◽

Pyruvate Carboxylase ◽

Specific Activity ◽

Rat Liver Mitochondria ◽

Rat Tissues ◽

Brown Adipose

1. Pyruvate carboxylase (EC 6.4.1.1), purified from rat liver mitochondria to a specific activity of 14 units/mg, was used for the preparation of antibodies in rabbits. 2. Tissue distribution studies showed that pyruvate carboxylase was present in all rat tissues that were tested, with considerable activities both in gluconeogenic tissues such as liver and kidney and in tissues with high rates of lipogenesis such as white adipose tissue, brown adipose tissue, adrenal gland and lactating mammary gland. 3. Immunochemical titration experiments with the specific antibodies showed no differences between the inactivation of pyruvate carboxylase from mitochondrial or soluble fractions of liver, kidney, mammary gland, brown adipose tissue or white adipose tissue. 4. The antibodies were relatively less effective in reactions against pyruvate carboxylase from sheep liver than against the enzyme from rat tissues. 5. Pyruvate carboxylase antibodies did not inactivate either propionyl-CoA carboxylase or acetyl-CoA carboxylase from rat liver. 6. It is concluded that pyruvate carboxylase in lipogenic tissues is similar antigenically to the enzyme in gluconeogenic tissues and that the soluble activities of pyruvate carboxylase detected in many rat tissues do not represent discrete enzymes but are the result of mitochondrial damage during tissue homogenization.

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Using RNA-Seq to Identify Reference Genes of the Transition from Brown to White Adipose Tissue in Goats

Animals ◽

10.3390/ani10091626 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1626

Author(s):

Linjie Wang ◽

Xingyue Chen ◽

Tianzeng Song ◽

Xujia Zhang ◽

Siyuan Zhan ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Reference Genes ◽

Rna Seq ◽

Sequencing Data ◽

Adipose Tissues ◽

Gene Normalization ◽

Brown Adipose ◽

Study Gene Expression

Brown adipose tissues have unique non-shivering thermogenesis functions, can be found in newborn ruminate animals, and then are gradually replaced by white adipose tissues in adulthood. For the purpose of exploring the intrinsic mechanism underlying the conversion process from brown (BAT) to white adipose tissue (WAT), it is necessary to utilize Quantitative PCR (qPCR) to study gene expression profiling. In this study, we identified reference genes that were consistently expressed during the transformation from goat BAT to WAT using RNA-seq data. Then, twelve genes were evaluated as candidate reference genes for qPCR in goat perirenal adipose tissue using three tools (geNorm, Normfinder, and BestKeeper). In addition, the selected reference genes were used to normalize the gene expression of PGC-1α and GPAT4. It was found that traditional reference genes, such as GAPDH, RPLP0, HPRT1, and PPIA were not suitable for target gene normalization. In contrast, CTNNB, PFDN5, and EIF3M, selected from RNA sequencing data, showed the least variation and were recommended as the best reference genes during the transformation from BAT to WAT.

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Photoperiodic regulation of gene expression in brown and white adipose tissue of Siberian hamsters (Phodopus sungorus)

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2002.282.1.r114 ◽

2002 ◽

Vol 282 (1) ◽

pp. R114-R121 ◽

Cited By ~ 23

Author(s):

Gregory E. Demas ◽

Robert R. Bowers ◽

Timothy J. Bartness ◽

Thomas W. Gettys

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Regulation Of Gene Expression ◽

Ribonuclease Protection Assay ◽

Peroxisome Proliferator ◽

Uncoupling Protein 1 ◽

Siberian Hamsters ◽

Brown Adipose

Siberian hamsters exhibit seasonal fluctuations in white adipose tissue (WAT) mass, with peaks in long “summerlike” days (LDs) and nadirs in short “winterlike” days (SDs). These responses can be mimicked in the laboratory after transfer from LDs to SDs. The purpose of the present study was to test whether changes in WAT and brown adipose tissue (BAT) gene expression that are mediated by the sympathetic nervous system in other obesity models are also associated with seasonal adiposity changes in Siberian hamsters. SDs decreased WAT mass and leptin mRNA, increased WAT β3-adrenoceptor mRNA, and induced retroperitoneal WAT uncoupling protein-1 mRNA (the latter measured by RT-PCR, others measured by ribonuclease protection assay) while increasing BAT uncoupling protein-1 and peroxisome proliferator-activated receptor-γ coactivator-1 mRNAs. These effects were not due to SD-induced gonadal regression and largely occurred before the usual SD-induced decreases in food intake. Thus the SD-induced decreased adiposity of Siberian hamsters may be due to a coordinated suite of WAT and BAT gene transcription changes ultimately increasing lipid mobilization and utilization.

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Increased expression level of ANGPTL8 in white adipose tissue under acute and chronic cold treatment

Lipids in Health and Disease ◽

10.1186/s12944-021-01547-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Hossein Arefanian ◽

Irina Al-Khairi ◽

Nermeen Abu Khalaf ◽

Preethi Cherian ◽

Sina Kavalakatt ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Cold Exposure ◽

Uncoupling Protein ◽

Cold Treatment ◽

Control Group ◽

Initial Increase ◽

Mrna Levels ◽

Brown Adipose

Abstract Background Angiopoietin-like proteins (ANGPTL), primarily 3, 4, and 8, play a major role in maintaining energy homeostasis by regulating triglyceride metabolism. This study evaluated the level of ANGPTL3, 4, and 8 in the liver, brown adipose tissue (BAT), and subcutaneous white adipose tissue (SAT) of mice maintained under acute and chronic cold conditions. Methods C57BL/6J mice were exposed to cold temperature (4 °C) for 10 days with food provided ad libitum. Animal tissues were harvested at Day 0 (Control group, n = 5) and Days 1, 3, 5, and 10 (cold treatment groups, n = 10 per group). The expression levels of various genes were measured in the liver, SAT, and BAT. ANGPTL3, 4, and 8 expressions were measured in the liver. ANGPTL4, 8, and genes involved in browning and lipid metabolism [uncoupling protein 1 (UCP1), lipoprotein lipase (LPL), and adipose triglyceride lipase (ATGL)] were measured in SAT and BAT. Western blotting (WB) analysis and immunohistochemistry (IHC) were performed to confirm ANGPTL8 expression in these tissues. Results The expressions of ANGPTL3 and 8 mRNA were significantly reduced in mouse liver tissues after cold treatment (P < 0.05); however, the expression of ANGPTL4 was not significantly altered. In BAT, ANGPTL8 expression was unchanged after cold treatment, whereas ANGPTL4 expression was significantly reduced (P < 0.05). ANGPTL4 levels were also significantly reduced in SAT, whereas ANGPTL8 gene expression exhibited over a 5-fold increase. Similarly, UCP1 gene expression was also significantly increased in SAT. The mRNA levels of LPL and ATGL showed an initial increase followed by a gradual decrease with an increase in the days of cold exposure. ANGPTL8 protein overexpression was further confirmed by WB and IHC. Conclusions This study shows that exposure to acute and chronic cold treatment results in the differential expression of ANGPTL proteins in the liver and adipose tissues (SAT and BAT). The results show a significant reduction in ANGPTL4 in BAT, which is linked to improved thermogenesis in response to acute cold exposure. ANGPTL8 was activated under acute and chronic cold conditions in SAT, suggesting that it is involved in regulating lipolysis and enhancing SAT browning.

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Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system

Biochemical Journal ◽

10.1042/bj3110729 ◽

1995 ◽

Vol 311 (3) ◽

pp. 729-733 ◽

Cited By ~ 199

Author(s):

P Trayhurn ◽

J S Duncan ◽

D V Rayner

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Lipoprotein Lipase ◽

White Adipose Tissue ◽

Critical Role ◽

Sympathetic System ◽

Obese Gene ◽

Ob Gene ◽

Brown Adipose ◽

White Fat

The effect of acute exposure to cold on the expression of the ob (obese) gene, which encodes a protein that plays a critical role in the regulation of energy balance and body weight, has been examined in epididymal white adipose tissue of mice. Overnight (18 h) exposure of mice to a temperature of 4 degrees C led to the disappearance of ob mRNA in epididymal white fat, and subsequent studies showed that a cold-induced loss of ob mRNA could occur in as little as 2-4 h of exposure to 4 degrees C. When mice exposed to cold for 18 h were returned to the warm (24 degrees C), there was a rapid stimulation of the expression of the ob gene, the mRNA returning within 2.5 h. Administration of noradrenaline led to a reduction in the level of ob mRNA in mice maintained in the warm, while isoprenaline resulted in the disappearance of the mRNA; these changes in ob mRNA were paralleled by similar changes in lipoprotein lipase mRNA. In contrast to white fat, the level of lipoprotein lipase mRNA in brown adipose tissue was increased by noradrenaline and isoprenaline. It is concluded that there is a cold-induced suppression of ob gene expression in white adipose tissue of mice and that this is mediated primarily by the sympathetic system. The profound effect of cold on ob gene expression indicates that the ob system relates to energy expenditure, as well as to satiety.

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Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Mechanisms of Ageing and Development ◽

10.1016/j.mad.2012.02.003 ◽

2012 ◽

Vol 133 (5) ◽

pp. 255-266 ◽

Cited By ~ 35

Author(s):

Naoyuki Okita ◽

Yusuke Hayashida ◽

Yumiko Kojima ◽

Mayumi Fukushima ◽

Keiko Yuguchi ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Brown Adipose ◽

Differential Responses

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Caloric Restriction and Hypothalamic Leptin Gene Therapy Have Differential Effects on Energy Partitioning in Adult Female Rats

International Journal of Molecular Sciences ◽

10.3390/ijms22136789 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6789

Author(s):

Russell T. Turner ◽

Carmen P. Wong ◽

Kristina M. Fosse ◽

Adam J. Branscum ◽

Urszula T. Iwaniec

Keyword(s):

Gene Therapy ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Female Rats ◽

Leptin Resistance ◽

Serum Leptin ◽

Brown Adipose

Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1 mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.

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Comprehensive Messenger Ribonucleic Acid Profiling Reveals That Peroxisome Proliferator-Activated Receptor γ Activation Has Coordinate Effects on Gene Expression in Multiple Insulin-Sensitive Tissues

Endocrinology ◽

10.1210/endo.142.3.8037 ◽

2001 ◽

Vol 142 (3) ◽

pp. 1269-1277 ◽

Cited By ~ 133

Author(s):

James M. Way ◽

W. Wallace Harrington ◽

Kathleen K. Brown ◽

William K. Gottschalk ◽

Scott S. Sundseth ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Expression Of Genes ◽

Brown Adipose ◽

Pparγ Agonists

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) agonists, including the glitazone class of drugs, are insulin sensitizers that reduce glucose and lipid levels in patients with type 2 diabetes mellitus. To more fully understand the molecular mechanisms underlying their therapeutic actions, we have characterized the effects of the potent, tyrosine-based PPARγ ligand GW1929 on serum glucose and lipid parameters and gene expression in Zucker diabetic fatty rats. In time-course studies, GW1929 treatment decreased circulating FFA levels before reducing glucose and triglyceride levels. We used a comprehensive and unbiased messenger RNA profiling technique to identify genes regulated either directly or indirectly by PPARγ in epididymal white adipose tissue, interscapular brown adipose tissue, liver, and soleus skeletal muscle. PPARγ activation stimulated the expression of a large number of genes involved in lipogenesis and fatty acid metabolism in both white adipose tissue and brown adipose tissue. In muscle, PPARγ agonist treatment decreased the expression of pyruvate dehydrogenase kinase 4, which represses oxidative glucose metabolism, and also decreased the expression of genes involved in fatty acid transport and oxidation. These changes suggest a molecular basis for PPARγ-mediated increases in glucose utilization in muscle. In liver, PPARγ activation coordinately decreased the expression of genes involved in gluconeogenesis. We conclude from these studies that the antidiabetic actions of PPARγ agonists are probably the consequence of 1) their effects on FFA levels, and 2), their coordinate effects on gene expression in multiple insulin-sensitive tissues.

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Modulation of Type I Iodothyronine 5’-Deiodinase Activity in white Adipose Tissue by Nutrition: Possible Involvement of Leptin

Physiological Research ◽

10.33549/physiolres.931866 ◽

2010 ◽

pp. 561-569

Author(s):

Z Macek Jílková ◽

S Pavelka ◽

P Flachs ◽

M Hensler ◽

V Kůs ◽

...

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Type I ◽

Metabolizing Enzymes ◽

Tissue Metabolism ◽

Brown Adipose ◽

Plasma Leptin ◽

White Fat

Adipose tissue is an important target for thyroid hormones (TH). However, the metabolism of TH in white adipose tissue is poorly characterized. Our objective was to describe possible changes in activities of TH-metabolizing enzymes in white adipose tissue, and the role of TH metabolism in the tissue during obesogenic treatment, caloric restriction and in response to leptin in mice. Activity of type I iodothyronine 5’-deiodinase (D1) in white fat was stimulated by a high-fat diet, which also increased plasma leptin levels, while brown adipose tissue D1 activity did not change. Caloric restriction decreased the activity of D1 in white fat (but not in the liver), reduced leptin levels, and increased the expression of stearoyl CoA desaturase 1 (SCD-1), a marker and mediator of the effect of leptin on tissue metabolism. Leptin injections increased D1 activity and down-regulated SCD-1 in white fat. Our results demonstrate changes in D1 activity in white adipose tissue under the conditions of changing adiposity, and a stimulatory effect of leptin on D1 activity in the tissue. These results suggest a functional role for D1 in white adipose tissue, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue.

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