The age-related inverse relationship between ob and lipogenic enzymes genes expression in rat white adipose tissue

We investigated acute effects of two allosteric protein kinase B (PKB) inhibitors, MK-2206 and Akti-1/2, on insulin-stimulated lipogenesis in rat epididymal adipocytes incubated with fructose as carbohydrate substrate. In parallel, the phosphorylation state of lipogenic enzymes in adipocytes and incubated epididymal fat pads was monitored by immunoblotting. Preincubation of rat epididymal adipocytes with PKB inhibitors dose-dependently inhibited the following: insulin-stimulated lipogenesis, increased PKB Ser473 phosphorylation, increased PKB activity and decreased acetyl-CoA carboxylase (ACC) Ser79 phosphorylation. In contrast, the effect of insulin to decrease the phosphorylation of pyruvate dehydrogenase (PDH) at Ser293 and Ser300 was not abolished by PKB inhibition. Insulin treatment also induced ATP-citrate lyase (ACL) Ser454 phosphorylation, but this effect was less sensitive to PKB inhibitors than ACC dephosphorylation by insulin. In incubated rat epididymal fat pads, Akti-1/2 treatment reversed insulin-induced ACC dephosphorylation, while ACL phosphorylation by insulin was maintained. ACL and ACC purified from white adipose tissue were poor substrates for PKBα in vitro. However, effects of wortmannin and torin, along with Akti-1/2 and MK-2206, on recognized PKB target phosphorylation by insulin were similar to their effects on insulin-induced ACL phosphorylation, suggesting that PKB could be the physiological kinase for ACL phosphorylation by insulin. In incubated epididymal fat pads from wild-type versus ACC1/2 S79A/S212A knockin mice, effects of insulin to increase lipogenesis from radioactive fructose or from radioactive acetate were reduced but not abolished. Together, the results support a key role for PKB in mediating insulin-stimulated lipogenesis by decreasing ACC phosphorylation, but not by decreasing PDH phosphorylation.

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Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj18.358 ◽

2018 ◽

Vol 22 (2) ◽

pp. 265-272 ◽

Cited By ~ 1

Author(s):

Y. V. Piskunova ◽

A. Y. Kazantceva ◽

A. V. Baklanov ◽

N. M. Bazhan

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Adipose Tissue ◽

Free Fatty Acids ◽

Glucose Uptake ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Age Related ◽

Brown Adipose ◽

Ay Mice

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice.

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SREBP-1c-Dependent Metabolic Remodeling of White Adipose Tissue by Caloric Restriction

International Journal of Molecular Sciences ◽

10.3390/ijms19113335 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3335 ◽

Cited By ~ 6

Author(s):

Masaki Kobayashi ◽

Namiki Fujii ◽

Takumi Narita ◽

Yoshikazu Higami

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Regulatory Element ◽

Whole Body ◽

Peroxisome Proliferator ◽

Master Regulator ◽

Beneficial Effects ◽

Age Related ◽

Metabolic Remodeling

Caloric restriction (CR) delays the onset of many age-related pathophysiological changes and extends lifespan. White adipose tissue (WAT) is not only a major tissue for energy storage, but also an endocrine tissue that secretes various adipokines. Recent reports have demonstrated that alterations in the characteristics of WAT can impact whole-body metabolism and lifespan. Hence, we hypothesized that functional alterations in WAT may play important roles in the beneficial effects of CR. Previously, using microarray analysis of WAT from CR rats, we found that CR enhances fatty acid (FA) biosynthesis, and identified sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA synthesis, as a mediator of CR. These findings were validated by showing that CR failed to upregulate factors involved in FA biosynthesis and to extend longevity in SREBP-1c knockout mice. Furthermore, we revealed that SREBP-1c is implicated in CR-associated mitochondrial activation through the upregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. Notably, these CR-associated phenotypes were observed only in WAT. We conclude that CR induces SREBP-1c-dependent metabolic remodeling, including the enhancement of FA biosynthesis and mitochondrial activation, via PGC-1α in WAT, resulting in beneficial effects.

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Age-Related Changes of Renin-Angiotensin System Genes in White Adipose Tissue of Rats

Hormone and Metabolic Research ◽

10.1055/s-2002-38238 ◽

2002 ◽

Vol 34 (11/12) ◽

pp. 716-720 ◽

Cited By ~ 3

Author(s):

F. Adams ◽

P. Wiedmer ◽

K. Gorzelniak ◽

S. Engeli ◽

S. Klaus ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Age Related ◽

Age Related Changes

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Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats

Biochemical Journal ◽

10.1042/bj2790303 ◽

1991 ◽

Vol 279 (1) ◽

pp. 303-308 ◽

Cited By ~ 37

Author(s):

L Pénicaud ◽

P Ferré ◽

F Assimacopoulos-Jeannet ◽

D Perdereau ◽

A Leturque ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Glucose Transporter ◽

Zucker Rats ◽

Lipogenic Enzymes ◽

Glut 4 ◽

Obese Rats ◽

Before And After ◽

Plasma Insulin Levels ◽

Obese Zucker Rats

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.

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Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Calorie Restriction During Aging

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa070 ◽

2020 ◽

Author(s):

Yunlu Sheng ◽

Fan Xia ◽

Lei Chen ◽

Yifan Lv ◽

Shan Lv ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

Metabolic Disorder ◽

Energy Homeostasis ◽

Nutritional Intervention ◽

Metabolic Health ◽

Protective Effects ◽

Age Related ◽

Brown Adipose

Abstract Age-related adipose tissue dysfunction is potentially important in the development of insulin resistance and metabolic disorder. Caloric restriction (CR) is a robust intervention to reduce adiposity, improve metabolic health, and extend healthy life span. Both white adipose tissue (WAT) and brown adipose tissue (BAT) are involved in energy homeostasis. CR triggers the beiging of WAT in young mice; however, the effects of CR on beiging of WAT and function of BAT during aging are unclear. This study aimed to investigate how age and CR impact the beiging of WAT, the function of BAT, and metabolic health in mice. C57BL/6 mice were fed CR diet (40% less than the ad libitum [AL] diet) for 3 months initiated in young (3 months), middle-aged (12 months), and old (19 months) stage. We found age-related changes in different types of adipose tissue, including adipocyte enlargement, declined beiging of WAT, and declined thermogenic and β-oxidational function of BAT. Moreover, CR attenuated age-associated adipocyte enlargement and prevented the age-related decline in beiging potential of WAT. These protective effects on the beiging potential were significant in inguinal WAT at all three ages, which were significant in epididymal WAT at young and old age. In contrast, thermogenic and β-oxidational function of BAT further declined after CR in the young age group. In conclusion, our findings reveal the contribution of WAT beiging decline to age-related metabolic disorder and suggest nutritional intervention, specifically targeting WAT beiging, as an effective approach to metabolic health during aging.

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Srebp-1c/Fgf21/Pgc-1α Axis Regulated by Leptin Signaling in Adipocytes—Possible Mechanism of Caloric Restriction-Associated Metabolic Remodeling of White Adipose Tissue

Nutrients ◽

10.3390/nu12072054 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2054

Author(s):

Masaki Kobayashi ◽

Seira Uta ◽

Minami Otsubo ◽

Yusuke Deguchi ◽

Ryoma Tagawa ◽

...

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Mitochondrial Biogenesis ◽

Molecular Mechanisms ◽

Whole Body ◽

Fibroblast Growth Factor 21 ◽

Leptin Signaling ◽

Age Related ◽

Metabolic Remodeling

Caloric restriction (CR) improves whole body metabolism, suppresses age-related pathophysiology, and extends lifespan in rodents. Metabolic remodeling, including fatty acid (FA) biosynthesis and mitochondrial biogenesis, in white adipose tissue (WAT) plays an important role in the beneficial effects of CR. We have proposed that CR-induced mitochondrial biogenesis in WAT is mediated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is transcriptionally regulated by sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA biosynthesis. We have also proposed that the CR-associated upregulation of SREBP-1 and PGC-1α might result from the attenuation of leptin signaling and the upregulation of fibroblast growth factor 21 (FGF21) in WAT. However, the detailed molecular mechanisms remain unclear. Here, we interrogate the regulatory mechanisms involving leptin signaling, SREBP-1c, FGF21, and PGC-1α using Srebp-1c knockout (KO) mice, mouse embryonic fibroblasts, and 3T3-L1 adipocytes, by altering the expression of SREBP-1c or FGF21. We show that a reduction in leptin signaling induces the expression of proteins involved in FA biosynthesis and mitochondrial biogenesis via SREBP-1c in adipocytes. The upregulation of SREBP-1c activates PGC-1α transcription via FGF21, but it is unlikely that the FGF21-associated upregulation of PGC-1α expression is a predominant contributor to mitochondrial biogenesis in adipocytes.

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Effects of high-carbohydrate diets on lipogenesis in rat interscapular brown adipose tissue

Biochemical Journal ◽

10.1042/bj2060667 ◽

1982 ◽

Vol 206 (3) ◽

pp. 667-669 ◽

Cited By ~ 2

Author(s):

P. John Weaire ◽

Tazeen F. Kanagasabai

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

White Bread ◽

Lipogenic Enzymes ◽

Adipose Tissues ◽

Interscapular Brown Adipose Tissue ◽

High Carbohydrate ◽

Brown Adipose

Cycloplasmic preparations from brown and white adipose tissues were assayed for three lipogenic enzymes throughout a programme of starvation followed by refeeding on either a normal or a white-bread diet. In the brown adipose tissue of rats fed on a white-bread diet the three enzymes were elevated to levels significantly higher than those in white adipose tissue.

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