Expression of ApoE Attenuates Differentiation of the White Adipose Tissue from ApoE-Knockout Diabetic Mice

JIANMIN RAN; XIAMING PAN; RUYI ZHANG; PING ZHU; RONGSHAO TAN; YAN LIU

doi:10.2337/db18-613-p

Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice

Journal of Translational Medicine ◽

10.1186/s12967-019-02166-1 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Bingxin Lu ◽

Jianing Zhong ◽

Jianfei Pan ◽

Xiaopeng Yuan ◽

Mingzhi Ren ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Energy Balance ◽

Glucose Metabolism ◽

Gene Transfer ◽

White Adipose Tissue ◽

High Fat Diet ◽

Diabetic Mice ◽

Metabolic Homeostasis ◽

High Fat

Abstract Background The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. Methods Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. Results Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-β/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. Conclusions These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

Download Full-text

lncRNA TUG1 promotes the brown remodeling of white adipose tissue by regulating miR‑204‑targeted SIRT1 in diabetic mice

International Journal of Molecular Medicine ◽

10.3892/ijmm.2020.4741 ◽

2020 ◽

Vol 46 (6) ◽

pp. 2225-2234

Author(s):

Ying Zhang ◽

Yuhang Ma ◽

Mingyu Gu ◽

Yongde Peng

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Diabetic Mice ◽

Lncrna Tug1

Download Full-text

Noradrenaline and ATP regulate white adipocyte adiponectin exocytosis: disturbed adrenergic and purinergic signalling in obesity-associated diabetes

10.1101/2021.08.19.456508 ◽

2021 ◽

Author(s):

Saliha Musovic ◽

Ali M. Komai ◽

Marina Kalds Said ◽

Yanling Wu ◽

Ingrid Wernstedt Asterholm ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Adrenergic Receptors ◽

Sympathetic Innervation ◽

Sympathetic Nerves ◽

Purinergic Signalling ◽

Diabetic Mice ◽

White Adipocyte ◽

Hmw Adiponectin ◽

Circulating Levels

AbstractWhite adipocyte adiponectin exocytosis is triggered by cAMP and a concomitant increase of cytosolic Ca2+ potentiates its release. White adipose tissue is richly innervated by sympathetic nerves co-releasing noradrenaline (NA) and ATP that may act on receptors in the adipocyte plasma membrane to increase cAMP via adrenergic receptors and Ca2+ via purinergic receptors, respectively. Here we determine the importance of NA and ATP for the regulation of white adipocyte adiponectin exocytosis, at the cellular and molecular level, and we specifically detail the ATP signalling pathway. Immunohistochemical staining demonstrates that tyrosine hydroxylase (enzyme involved in catecholamine synthesis) is dramatically reduced in inguinal white adipose tissue (IWAT) isolated from mice with diet-induced obesity; this is associated with diminished levels of NA in IWAT and with lowered serum adiponectin. Adiponectin exocytosis (measured as increase in plasma membrane capacitance and as secreted product) is triggered by NA or ATP alone in cultured and primary mouse IWAT adipocytes, and enhanced by a combination of the two secretagogues. The ATP-induced adiponectin exocytosis is largely Ca2+-dependent and activated via P2Y2 receptors (P2Y2Rs) and the Gq11/PLC pathway. Adiponectin release induced by the nucleotide is abrogated in adipocytes isolated from obese/diabetic mice and this is associated with ∼70% reduced abundance of P2Y2Rs. The NA-triggered adiponectin exocytosis is likewise abolished in “obese adipocytes”, concomitant with a 50% lower gene expression of beta 3 adrenergic receptors (β3ARs). The NA-stimulated adiponectin secretion does not contain Ca2+-dependent components. Collectively, our data suggest that sympathetic innervation is a principal regulator of adiponectin exocytosis and that disruptions of this control are associated with the obesity-associated reduction of circulating levels of HMW adiponectin.Key point listWhite adipose tissue is richly innervated by sympathetic nerves that co-release noradrenaline (NA) and ATP.Protein levels of tyrosine hydroxylase and NA are dramatically decreased in white adipose tissue from obese/diabetic mice, concomitant with reduced serum levels of high-molecular weight (HMW) adiponectin.NA and ATP stimulate white adipocyte adiponectin exocytosis via beta adrenergic and purinergic receptors respectively. The ATP-induced adiponectin secretion is chiefly Ca2+-dependent and activated via the P2Y2/Gq11/PLC pathway.The purinergic signalling is abrogated in adipocytes from obese/diabetic mice, due to reduced abundance of P2Y2Rs. The response to NA is likewise abolished in “obese adipocytes”, associated with lowered gene expression of beta 3 adrenergic receptors (β3ARs).We propose that sympathetic innervation is central in regulation of adiponectin exocytosis via co-secretion of NA and ATP and that this control is disrupted in obesity-associated diabetes, leading to lower circulating levels of HMW adiponectin.

Download Full-text