Dataset Information

Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice.

ABSTRACT: The in vivo role of mechanistic target of rapamycin (mTOR) in the development and function of adipose tissue, especially brown adipose tissue (BAT), is not well understood. Here, we aimed to assess the effect of mTOR (also known as Mtor) knockout on adipose tissues and systemic energy metabolism.We generated adipocyte-specific mTOR-knockout mice (Adipoq-mTOR) by crossing adiponectin-Cre (Adipoq-Cre) mice with mTOR (flox/flox) mice. The mice were then subjected to morphological, physiological (indirect calorimetry, glucose and insulin tolerance tests) and gene expression analyses to determine the role of mTOR in adipose tissues.We provide in vivo evidence that mTOR is essential for adipose tissue development and growth. Deletion of mTOR decreased the mass of both BAT and white adipose tissues (WAT) and induced browning of WAT. In addition, ablation of mTOR in adipose tissues caused insulin resistance and fatty liver in the Adipoq-mTOR mice. Furthermore, mTOR was required for adipocyte differentiation in vivo and activation of PPAR? ameliorated the differentiation deficiency of the mTOR-null adipocytes.Our findings demonstrate that mTOR is a critical regulator of adipogenesis and systemic energy metabolism. Our study provides key insights into the role of mTOR in adipose tissues; such knowledge may facilitate the development of novel strategies with which to treat obesity and related metabolic diseases.

SUBMITTER: Shan T

PROVIDER: S-EPMC5345851 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice.

Shan Tizhong T Zhang Pengpeng P Jiang Qinyang Q Xiong Yan Y Wang Yizhen Y Kuang Shihuan S

Diabetologia 20160613 9

<h4>Aims/hypothesis</h4>The in vivo role of mechanistic target of rapamycin (mTOR) in the development and function of adipose tissue, especially brown adipose tissue (BAT), is not well understood. Here, we aimed to assess the effect of mTOR (also known as Mtor) knockout on adipose tissues and systemic energy metabolism.<h4>Methods</h4>We generated adipocyte-specific mTOR-knockout mice (Adipoq-mTOR) by crossing adiponectin-Cre (Adipoq-Cre) mice with mTOR (flox/flox) mice. The mice were then subje ...[more]

PMID: 27294611

Similar Datasets

Project description:Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2 (-/-)) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2 (-/-) mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2 (-/-) mice until 6?months of age; however, by 10?months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2 (-/-) mice by 2?months, but peaked by 6?months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2 (-/-) mice had reduced trabecular bone volume by 2?months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2 (-/-) mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2 (-/-) mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity.

Dataset Information

Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice.

Publications

Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets