scholarly journals Prevention of Adipose Tissue Depletion during Food Deprivation in Angiotensin Type 2 Receptor-Deficient Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5078-5086 ◽  
Author(s):  
Laurent Yvan-Charvet ◽  
Patrick Even ◽  
Noël Lamandé ◽  
Pascal Ferré ◽  
Annie Quignard-Boulangé
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Physiological Role ◽  
Acid Oxidation ◽  
Ang Ii ◽  
Wild Type ◽  
Angiotensin Type 2 Receptor

Angiotensin (Ang) II is produced locally in various tissues, but its role in the regulation of tissue metabolism is still unclear. Recent studies have revealed the role of type 2 Ang II receptor (AT2R) in the control of energy homeostasis and lipid metabolism. The contribution of the AT2R to adaptation to starvation was tested using AT2R-deficient (AT2Ry/−) mice. Fasted AT2Ry/− mice exhibited a lower loss of adipose tissue weight associated to a decreased free fatty acid (FFA) release from stored lipids than the controls. In vitro studies show that Ang II causes an AT1R-mediated antilipolytic effect in isolated adipocytes. AT1R expression is up-regulated by fasting in both genotypes, but the increase is more pronounced in AT2Ry/− mice. In addition, the increased muscle β-oxidation displayed in AT2Ry/− mice on a fed state, persists after fasting compared with wild-type mice. In liver from fed mice, AT2R deficiency did not modify the expression of genes involved in fatty acid oxidation. However, in response to fasting, the large increase of the expression of this subset of genes exhibited by wild-type mice, was impaired in AT2Ry/− mice. Taken together, decreased lipolytic capacity and increased muscle fatty acid oxidation participate in the decreased plasma FFA observed in fasted AT2Ry/− mice and could account for the lower FFA metabolism in the liver. These data reveal an important physiological role of AT2R in metabolic adaptations to fasting.

Effect of adipocyte β3-adrenergic receptor activation on the type 2 diabetic MKR mice

2006 ◽  
Vol 290 (6) ◽  
pp. E1227-E1236 ◽  
Author(s):  
Hyunsook Kim ◽  
Patricia A. Pennisi ◽  
Oksana Gavrilova ◽  
Stephanie Pack ◽  
William Jou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Receptor Activation ◽  
Whole Body ◽  
Acid Oxidation ◽  
Adrenergic Agonists ◽  
Nonobese Diabetic ◽  
Type 2 Diabetic

The antiobesity and antidiabetic effects of the β3-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β3-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β3-adrenergic agonists in nonobese diabetic subjects.

scholarly journals Importance of experimental conditions in evaluating the malonyl-CoA sensitivity of liver carnitine acyltransferase. Studies with fed and starved rats

1981 ◽  
Vol 200 (2) ◽  
pp. 217-223 ◽  
Author(s):  
J D McGarry ◽  
D W Foster
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Rat Liver ◽  
Competitive Inhibition ◽  
Physiological Role ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa

The experiments reconfirm the powerful inhibitory effect of malonyl-CoA on carnitine acyltransferase I and fatty acid oxidation in rat liver mitochondria (Ki 1.5 microM). Sensitivity decreased with starvation (Ki after 18 h starvation 3.0 microM, and after 42 h 5.0 microM). Observations by Cook, Otto & Cornell [Biochem. J. (1980) 192, 955--958] and Ontko & Johns [Biochem. J. (1980) 192, 959--962] have cast doubt on the physiological role of malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. The high Ki values obtained in the cited studies are shown to be due to incubation conditions that cause substrate depletion, destruction of malonyl-CoA or generation of excessively high concentrations of unbound acyl-CoA (which offsets the competitive inhibition of malonyl-CoA towards carnitine acyltransferase I). The present results are entirely consistent with the postulated role of malonyl-CoA as the primary regulatory of fatty acid synthesis and oxidation in rat liver.

scholarly journals Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

2015 ◽  
Vol 308 (9) ◽  
pp. E756-E769 ◽  
Author(s):  
Maria Ida Malandrino ◽  
Raquel Fucho ◽  
Minéia Weber ◽  
María Calderon-Dominguez ◽  
Joan Francesc Mir ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Human Adipose Tissue ◽  
Acid Oxidation ◽  
Mutant Form ◽  
Adenoviral Infection ◽  
Triglyceride Accumulation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.

scholarly journals Chronic cold exposure induces autophagy to promote fatty acid oxidation, mitochondrial turnover, and thermogenesis in brown adipose tissue

iScience ◽  
2021 ◽  
pp. 102434
Author(s):  
Winifred W. Yau ◽  
Kiraely Adam Wong ◽  
Jin Zhou ◽  
Nivetha Kanakaram Thimmukonda ◽  
Yajun Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Oxidation ◽  
Cold Exposure ◽  
Acid Oxidation ◽  
Brown Adipose ◽  
Mitochondrial Turnover

scholarly journals Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-induced Weight Gain in Male Mice

2020 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Weight Gain ◽  
Energy Metabolism ◽  
Energy Balance ◽  
Fatty Acid Oxidation ◽  
Positive Energy ◽  
Acid Oxidation ◽  
Male Mice ◽  
Short Term

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.

Abstract P288: Systemic Administration of an Angiotensin Type-2 Receptor Agonist Decreases Renal Regulatory T Cells

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ellen E Gillis ◽  
Jennifer C Sullivan
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Critical Role ◽  
High Dose ◽  
Ang Ii ◽  
Osmotic Minipump ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

There is increasing evidence supporting a critical role of the immune system in the development of hypertension. Our lab has previously reported sex differences in the renal T cell profile in both Spontaneously Hypertensive Rats (SHR) and Angiotensin II (Ang II) models of hypertension, with females having more anti-inflammatory regulatory T cells (Tregs) than males. Ang II has a well-defined role in the activation of pro-inflammatory T cells in hypertension via the angiotensin type-1 receptor (AT1R). Less is known about the role of the angiotensin type-2 receptor (AT2R) in the regulation of immune cells, although the AT2R has been shown to be cardioprotective and AT2R expression is greater in females than males. Based on the potential anti-hypertensive role of AT2Rs, we hypothesized that administration of an AT2R agonist, Compound 21 (C21), would increase renal Tregs, and this increase would be greater in females due to greater AT2R expression. Male and female SHR (10 weeks of age, n=3-4) were implanted with telemetry units for continuous monitoring of mean arterial pressure (MAP). Following 10 days of recovery, baseline MAP was recorded for 5 days. Rats were then divided into the following treatment groups: surgical controls, low dose C21 (150 ng/kg/min, sc by osmotic minipump), high dose C21 (300 ng/kg/min, sc by osmotic minipump). Kidneys were harvested after 2 weeks of treatment and flow cytometry was performed on whole kidney homogenates. MAP was not altered by C21 treatment in males (137±4 vs 134±4 vs 134±4 mmHg; n.s.) or females (128±2 vs 136±5 vs 134±4 mmHg; n.s.). Interestingly, despite having no effect on MAP, there was a significant decrease in renal CD3 + CD4 + FoxP3 + Tregs in females following both low and high doses of C21 (data expressed as % CD3 + CD4 + cells: 6±0.6 vs 3±0.6 vs 3.5±1.3 %, respectively; p=0.02). Tregs decrease in males following the high dose of C21 only (data expressed as % CD3 + CD4 + cells: 3.3±0.3 vs 3.3±0.5 vs 1.7±0.7 %, respectively; p=0.05). Total CD3 + T cells, CD3 + CD4 + T cells, and Th17 cells were not altered by C21 treatment. In conclusion, AT2R activation suppresses renal Tregs, and females are more sensitive than males. These data suggest a novel role for AT2R regulation in the kidney in hypertension.

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