Recruitment and remodeling of peridroplet mitochondria in human adipose tissue

Abstract

Beige adipocyte mitochondria contribute to thermogenesis by uncoupling and by ATP-consuming futile cycles. Since uncoupling may inhibit ATP synthesis, it is expected that expenditure through ATP synthesis is segregated to a disparate population of mitochondria. Recent studies in mouse brown adipocytes identified peridroplet mitochondria (PDM) as having greater ATP synthesis and pyruvate oxidation capacities, while cytoplasmic mitochondria have increased fatty acid oxidation and uncoupling capacities. However, the occurrence of PDM in humans and the processes that result in their expansion have not been elucidated. Here, we describe a novel high-throughput assay to quantify PDM that is successfully applied to white adipose tissue from mice and humans. Using this approach, we found that PDM content varies between white and brown fat in both species. We used adipose tissue from pheochromocytoma (Pheo) patients as a model of white adipose tissue browning, which is characterized by an increase in the capacity for energy expenditure. In contrast with control subjects, PDM content was robustly increased in the periadrenal fat of Pheo patients. Remarkably, bioenergetic changes associated with browning were primarily localized to PDM compared to cytoplasmic mitochondria (CM). PDM isolated from periadrenal fat of Pheo patients had increased ATP-linked respiration, Complex IV content and activity, and maximal respiratory capacity. We found similar changes in a mouse model of re-browning where PDM content in whitened brown adipose tissue was increased upon re-browning induced by decreased housing temperature. Taken together, this study demonstrates the existence of PDM as a separate functional entity in humans and that browning in both mice and humans is associated with a robust expansion of peri-droplet mitochondria characterized by increased ATP synthesis linked respiration.

ADRA1A–Gαq signalling potentiates adipocyte thermogenesis through CKB and TNAP

“…Letter https://doi.org/10.1038/s42255-022-00667-w that ADRA1A stimulation potentiates cAMP-induced thermogenesis in a UCP1-independent manner. The identification of distinct adipocyte subtypes [32][33][34][35][36] and mitochondrial heterogeneity within thermogenic fat cells 37 suggests that discrete thermogenic pathways could segregate inter-cellularly or intracellularly. Ckb and Alpl are expressed in Ucp1 + adipocytes 2,3 , and we demonstrate that genetic or pharmacological inhibition of their protein products decreases thermogenesis in brown adipocytes in the presence of UCP1.…”

What Is the Role of Gut Microbiota in Obesity Prevalence? A Few Words about Gut Microbiota and Its Association with Obesity and Related Diseases

“…There are two main types of adipose tissue distinguished in human body-white adipose tissue (WAT) and brown adipose tissue (BAT) [26]. Their content in the organism depends on genetic, metabolic, and environmental factors, but WAT makes up the majority of adipose tissue in adults [27].…”

Effects of Aerobic Exercise in Hepatic Lipid Droplet-Mitochondria interaction in Non-alcoholic Fatty Liver Disease

“…Analyses of the liver were performed using Fiji/ImageJ software (National Institutes of Health, Bethesda, MD). Since the LD-mitochondria interaction is described as adherence rather than proximity (25,30), physical contact between the edge of the LD surface and the outer membrane of the mitochondrion by electron microscopy was considered LD-mitochondria interaction. In addition, a high electron density is often observed at the site of contact between the two organelles.…”