Autophagic Clearance of Lipid Droplets Alters Metabolic Phenotypes in a Genetic Obesity–Diabetes Mouse Model

Abstract

Lipid droplets (LDs) are intracellular organelles that store neutral lipids, and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and diabetes. Meanwhile, the potential pathological contributions of LDs in these diseases are unclear, likely due to a lack of chemical biology tools to clear LDs. We recently developed LD-clearance small molecule compounds, Lipid Droplets·AuTophagy TEthering Compounds (LD·ATTECs), that are able to induce autophagic clearance of LDs in cells and in the liver of db/db (C57BL/6J Leprdb/Leprdb) mouse model, which is a widely used genetic model for obesity–diabetes. Meanwhile, the potential effects on the metabolic phenotype remain to be elucidated. Here, using the metabolic cage assay and the blood glucose assay, we performed phenotypic characterization of the effects of the autophagic degradation of LDs by LD·ATTECs in the db/db mouse model. The study reveals that LD·ATTECs increased the oxygen uptake of mice and the release of carbon dioxide, enhanced the heat production of animals, partially enhanced the exercise during the dark phase, decreased the blood glucose level and improved insulin sensitivity. Collectively, the study characterized the metabolic phenotypes induced by LD·ATTECs in an obesity–diabetes mouse model, revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity–diabetes pathogenesis from the phenotypic perspective.

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

“…Recently, maternal obesity has also been identified as a risk factor for CHD (Persson et al , 2019). Since the phenotype overlaps between obesity and diabetes, it is yet to be elucidated whether obesity increases the CHD risk mediated by promoting diabetes, or whether it damages the developing heart through dyslipidemia and other secondary effects including hyperinsulinemia, insulin resistance, and oxidative stress (Helle & Priest, 2020; Chen et al , 2023a). Here, we found lipids, including LDL and total TC, were upregulated in the CHD group, and the cell‐type immune enrichment suggested the enrichment of adipocytes and pre‐adipocytes in the CHD group.…”

Exercise Alleviates Aging of Adipose Tissue through Adipokine Regulation

“…Emerging evidence suggests that exercise (e.g., resistance exercise, endurance exercise) is a highly effective intervention in alleviating obesity and plays a significant role in individual metabolism, as evidenced by its impact on the morphology and function of adipose depots [ 4 , 5 , 6 , 7 , 8 , 9 ]. Moreover, circulating factors induced by exercise (e.g., swimming exercise, voluntary wheel-running exercise), known as exerkines, are involved in the metabolism of AT in response to aging [ 7 , 10 , 11 , 12 , 13 ]. The goal of this review is to offer a comprehensive overview of the benefits of regular exercise in counteracting age-related declines in AT function.…”

Serum Metabolomic and Lipidomic Profiling Reveals the Signature for Postoperative Obesity among Adult-Onset Craniopharyngioma

“…A definitive diagnosis requires surgical pathology. Craniopharyngioma accounts for 1.2–4.6% of all brain tumors, yet they exhibit a notably higher recurrence rate compared to pituitary tumors [ 2 , 3 ]. At present, surgery is the principal treatment, supplemented by radiotherapy.…”