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LH induces de novo cholesterol biosynthesis via SREBP activation in granulosa cells during ovulation in female mice
In this study, when immature mice were treated with gonadotropins (eCG followed by hCG), eCG induced and hCG maintained the expression of SREBP-1a, -2, and SCAP granulosa cells, whereas INSIG1 expression was dramatically downregulated after hCG injection. Downregulation of INSIG1 led to generate the SREBPs active form and translocate the SREBPs active form to nuclei. Inhibition of generation of the SREBPs active form by fatostatin or Scap siRNA in both in vivo and in vitro significantly decreased the expressions of de novo cholesterol biosynthetic enzymes, cholesterol accumulation, and progesterone (P4) production compared...
Source: Endocrinology - August 25, 2021 Category: Endocrinology Authors: Tomoya Nakanishi Risa Tanaka Shingo Tonai Joo Yeon Lee Manami Yamaoka Tomoko Kawai Asako Okamoto Masayuki Shimada Yasuhisa Yamashita Source Type: research

An RNAi screening of clinically relevant transcription factors regulating human adipogenesis and adipocyte metabolism
CONCLUSIONS: This comprehensive RNAi screening in hASC suggests that a large proportion of WAT TFs that are impacted by metabolic conditions might be important for hyperplastic adipose tissue expansion. The screen also identified JARID2 as a novel TF essential for the development of functional adipocytes.PMID:33963396 | DOI:10.1210/endocr/bqab096
Source: Endocrinology - May 8, 2021 Category: Endocrinology Authors: Christel Bj örk Narmadha Subramanian Jianping Liu Juan Ramon Acosta Beatriz Tavira Anders B Eriksson Peter Arner Jurga Laurencikiene Source Type: research

Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice.
Abstract Sphingosine 1-phosphate (S1P) is known to regulate insulin resistance in hepatocytes, skeletal muscle cells, and pancreatic β-cells. Among its five cognate receptors (S1pr1-5), S1P seems to counteract insulin signaling and confer insulin resistance via S1pr2 in these cells. S1P may also regulate insulin resistance in adipocytes, but the S1pr subtype(s) involved remains unknown. Here we investigated systemic glucose/insulin tolerance and phenotypes of epididymal adipocytes in high-fat diet-fed wild-type and S1pr2-deficient (S1pr2(-/-)) mice. Adult S1pr2(-/-) mice displayed smaller body/epididymal fat tiss...
Source: Endocrinology - March 4, 2016 Category: Endocrinology Authors: Kitada Y, Kajita K, Taguchi K, Mori I, Yamauchi M, Ikeda T, Kawashima M, Asano M, Kajita T, Ishizuka T, Banno Y, Kojima I, Chun J, Kamata S, Ishii I, Morita H Tags: Endocrinology Source Type: research

The glucose sensor ChREBP links de-novo lipogenesis to PPARγ activity and adipocyte differentiation.
Abstract Reduced de-novo lipogenesis (DNL) in adipose tissue, often observed in obese individuals, is thought to contribute to insulin resistance. Besides trapping excess glucose and providing for triglycerides and energy storage, endogenously synthesized lipids can function as potent signaling molecules. Indeed, several specific lipids and their molecular targets that mediate insulin sensitivity have been recently identified. Here we report that carbohydrate element binding protein (ChREBP), a transcriptional inducer of glucose utilization and DNL, controls the activity of the adipogenic master regulator peroxiso...
Source: Endocrinology - July 16, 2015 Category: Endocrinology Authors: Witte N, Muenzner M, Rietscher J, Knauer M, Heidenreich S, Nuotio-Antar AM, Graef FA, Fedders R, Tolkachov A, Goehring I, Schupp M Tags: Endocrinology Source Type: research

Depression of type I diacylglycerol kinases in pancreatic β-cells from male mice results in impaired insulin secretion.
This study investigated the expression and function of DGK in pancreatic β-cells. mRNA expression of type I DGK isoforms (α, β, γ) was detected in mouse pancreatic islets and the β-cell line MIN6. Protein expression of DGKα and γ was also detected in mouse β-cells and MIN6 cells. The type I DGK inhibitor R59949 inhibited high K(+)- and glucose-induced insulin secretion in MIN6 cells. Moreover, single knockdown of DGKα or γ by siRNA slightly but significantly decreased glucose- and high K(+)-induced insulin secretions, and the double knockdown further decreased them to the levels comparable to those induced by R59...
Source: Endocrinology - September 13, 2013 Category: Endocrinology Authors: Kurohane Kaneko Y, Kobayashi Y, Motoki K, Nakata K, Miyagawa S, Yamamoto M, Hayashi D, Shirai Y, Sakane F, Ishikawa T Tags: Endocrinology Source Type: research

Antioxidant N-acetylcysteine protects pancreatic β-cells against aldosterone-induced oxidative stress and apoptosis in female db/db mice and insulin-producing MIN6 cells.
This study aimed to investigate whether oxidative stress is involved in and whether the antioxidant N-acetylcysteine (NAC) or the mineralocorticoid receptor (MR) antagonist spironolactone could prevent or delay β-cell damage in vivo and in vitro. As expected, 8 weeks after aldosterone treatment, 12-week-old female diabetic db/db mice exhibited impaired oral glucose tolerance, decreased β-cell mass, and heightened levels of oxidative stress marker (urinary 8-OHdG). NAC reversed these symptoms completely, whereas spironolactone treatment did so only partially. After exposure to aldosterone, the mouse pancreatic β-cell lin...
Source: Endocrinology - September 5, 2013 Category: Endocrinology Authors: Jin HM, Zhou DC, Gu HF, Qiao QY, Fu SK, Liu XL, Pan Y Tags: Endocrinology Source Type: research

Knockdown of RyR3 Enhances Adiponectin Expression Through an atf3-Dependent Pathway.
In this study, we identified that ryanodine receptor (RyR)3 plays an important role in the regulation of adiponectin expression. RyR3 was expressed in 3T3-L1 preadipocytes, and its level was decreased upon adipogenesis. Silencing of RyR3 expression in 3T3-L1 preadipocytes resulted in up-regulated adiponectin promoter activity, enhanced adiponectin mRNA expression, and more adiponectin protein secreted into the medium. An inverse relation between RyR3 and adiponectin mRNA levels was also observed in adipose tissues of db/db mice. In addition, knockdown of RyR3 with small interfering RNA (siRNA) in db/db mice and high-fat di...
Source: Endocrinology - February 6, 2013 Category: Endocrinology Authors: Tsai SH, Chang EY, Chang YC, Hee SW, Tsai YC, Chang TJ, Chuang LM Tags: Endocrinology Source Type: research