Volume 4 Issue 8, August 2022

Adipose tissue plays a critical role in systemic metabolism. This work describes how perturbations in the adipocyte progenitor cell repertoire during the perinatal period exert long-lasting metabolic effects in adulthood.

New research shows that a drug conjugate that links the dual PPAR𝛼/𝛾 agonist tesaglitazar to a GLP-1 receptor agonist has superior effects on weight loss and glucose metabolism compared with monotherapy in mice. The conjugate has actions in the hypothalamus that may contribute to its benefits.

New research reports that targeting the asialoglycoprotein receptor (ASGR1) in mice promotes cholesterol excretion through a mechanism involving stabilization of LXR without lipogenesis activation, strengthening the idea of therapeutically targeting ASGR1 to lower blood cholesterol and risk of atherosclerotic cardiovascular disease.

The authors of this Perspective summarize the state of human islet research and compare available islet procurement methods, proposing strategies to increase collaboration and standardization to accelerate discoveries on diabetes.

Measurements of oxygen consumption rates have been central to the resurgent interest in studying cellular metabolism. To enhance the overall reproducibility and reliability of these measurements, Divakaruni and Jastroch provide a guide advising on the selection of experimental models and instrumentation as well as the analysis and interpretation of data.

A single transfer of blood from old male mice is shown to induce cellular and tissue senescence in young animals, unless old mice are treated with senolytic drugs before blood exchange.

Baboota et al. investigate senescence as a driver of human NAFLD/NASH and show the roles of BMP4 and its antagonist Gremlin 1 as anti-senescent and pro-senescent molecules, respectively.

Alterations in cholesterol homeostasis may contribute to hepatic cancer aggressiveness. Liu, Tian, and Zhang et al. identify the long non-coding RNA SNHG6 as an important player in this process by linking cholesterol sensing with cancer cell growth through mTORC1 signaling.

RNA modifications have emerged as important regulators of RNA function. In this study, Peng, Chen, Wei and Guo et al. show that the 18S rRNA N⁶-methyladenosine methyltransferase complex METTL5–TRMT112 regulates hepatic lipid metabolism and contributes to hepatocellular carcinoma.

Zhang et al. use single-cell transcriptomics to map the cellular landscape of perinatal murine epididymal adipose tissue, and demonstrate that altering the adipogenic capacity of perinatal adipose progenitors has long-term effects on progenitor plasticity, tissue expandability and metabolic health in adulthood.

A conjugate drug consisting of GLP-1 receptor agonist and the PPARɑ/ɣ dual-agonist tesaglitazar is shown to have superior anti-diabetic effects than monotherapy.