bims-mimbat 2022-08-28 papers

Diabetes. 2022 Aug 24. pii: db220205. [Epub ahead of print]

miR-130b/301b is a Negative Regulator of Beige Adipogenesis and Energy Metabolism in vitro and in vivo.

Wenyi Luo, Youngsil Kim, Mary Ellen Jensen, Oana Herlea-Pana, Weidong Wang, Michael C Rudolph, Jacob E Friedman, Steven D Chernausek, Shaoning Jiang.

Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity and related metabolic complications. The microRNA cluster, miR-130b/301b, is highly expressed in adipose tissues and has been implicated in metabolic diseases as a post-transcriptional regulator of mitochondrial biogenesis and lipid metabolism. We investigated the roles of miR-130b/301b in regulating beige adipogenesis in vivo and in vitro. miR-130b/301b declined in adipose progenitor cells during beige adipogenesis, while forced overexpression of miR-130b-3p or miR-301b-3p suppressed uncoupling protein 1 (UCP1) and mitochondrial respiration, suggesting a decline in miR-130b-3p or miR-301b-3p is required for adipocyte precursors to develop the beige phenotype. Mechanistically, miR-130b/301b directly targeted AMP-activated protein kinase (AMPKα1) and suppressed peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), key regulators of brown adipogenesis and mitochondrial biogenesis. Mice lacking the miR-130b/301b microRNA cluster showed reduced visceral adiposity and less weight gain. miR-130b/301b null mice exhibited improved glucose tolerance, increased UCP1 and AMPK activation in subcutaneous fat (iWAT), and increased response to cold-induced energy expenditure. Together, these data identify the miR-130b/301b cluster as a new regulator that suppresses beige adipogenesis involving PGC-1α and AMPK signaling in iWAT and is therefore a potential therapeutic target against obesity and related metabolic disorders.

DOI: https://doi.org/10.2337/db22-0205

FASEB J. 2022 Sep;36(9): e22510

The fates of different types of adipose tissue after transplantation in mice.

Shenglu Jiang, Jiayan Lin, Qian Zhang, Yunjun Liao, Feng Lu, Junrong Cai.

Fat grafting is one of the most commonly applied procedure for soft-tissue repair. However, it remains unclear whether the type of adipose tissue would have any effects on fat graft survival. The present study aimed to determine fates of fat grafting of three different types of fat tissue. In this study, mice were randomly divided into three groups, white adipose tissue (WAT) group, beige adipose tissue (beige AT) group and brown adipose tissue (BAT) group. Before transplantation, donor mice were injected with rosiglitazone or phosphate-buffered saline (PBS). The WAT and BAT were obtained from PBS-treated mice while beige AT was obtained from the rosiglitazone-treated mice. Three types of fat tissue (150 mg each) were transplanted in three groups, respectively, and harvested at 2, 4 or 12 weeks. The BAT and beige AT contained smaller adipocytes and expressed higher level of uncoupling protein-1 gene. The retention rate of the transplanted fat was significantly higher for beige than for white fat, but was significantly lower for brown than for white fat. Transplanted brown fat was characterized by upregulated inflammation and high endoplasmic reticulum stress. By contrast, fat grafts in beige AT group showed the best adipogenic capacity, moderate inflammation level and superior angiongenesis. In vitro, under hypoxic condition, fewer apoptotic cells were found in beige adipocyte group than that in brown and white adipocyte group. Conditioned medium from brown adipocytes induced M1 polarization of RAW 264.7 macrophages while that from beige adipocytes effectively promoted M2 polarization. Therefore, we suggest that beige AT provides a new potential choice for fat grafting because of low inflammation and superior survival but BAT might not be ideal for fat grafting due to its poor survival.

Keywords: beige adipose tissue; brown adipose tissue; fat grafting; white adipose tissue

DOI: https://doi.org/10.1096/fj.202200408R

J Exp Biol. 2022 Aug 25. pii: jeb.244502. [Epub ahead of print]

Seasonal adjustments in body mass and basal thermogenesis in Chinese hwameis (Garrulax canorus): the roles of temperature and photoperiod.

Chenxing Li, Chenyu Liu, Pingxia Hu, Xiyu Zheng, Ming Li, Jinsong Liu.

For small birds to survive during seasonal acclimatization in temperate zones, regulation of body mass and thermogenesis is crucial. To determine the role of temperature and photoperiod in seasonal changes in body mass and thermogenesis in Chinese hwameis (Garrulax canorus), we compared body mass, basal metabolic rate (BMR), energy intake and cellular metabolic capacity of the tissue (muscle) and/ or organs (liver, kidney, heart and small intestine) in seasonally acclimatized and laboratory acclimated hwameis. A significant seasonal influence on body mass and BMR (which peaked in winter) was found, and these variations were mirrored by exposing the housed birds to cold temperatures or a short photoperiod. The level of dry matter intake, gross energy intake and digestible energy intake were higher during winter, and in housed animals that were exposed to cold temperatures. These results suggest that by increasing energy intake and thermogenesis, Chinese hwameis can overcome winter thermoregulatory challenges. When compared with warm-acclimated birds, cold-acclimated birds displayed higher mass-specific and whole-organ state 4 respiration in the muscle, liver and kidney, and higher mass-specific and whole-organ cytochrome c oxidase activity in the liver. These data demonstrated that the cellular thermogenesis partly underpins basal thermoregulation in Chinese hwameis. Cold temperature and short photoperiod can be used as helpful environmental cues during seasonal acclimatization. However, the role of temperature is more significant compared with that of photoperiod in Chinese hwameis, the changes in energy metabolism and thermoregulation induced by temperature appear to be intensified by photoperiod.

Keywords: Basal metabolic rate; Chinese hwameis (Garrulax canorus); Cytochrome c oxidase; Energy intake; State 4 respiration

DOI: https://doi.org/10.1242/jeb.244502

Adipocyte. 2022 Aug 24.

Comparative transcriptomic analysis of rabbit interscapular brown adipose tissue whitening under physiological conditions.

Lei Li, Qian Wan, Qiaoyun Long, Tao Nie, Shiting Zhao, Liufeng Mao, Chuanli Cheng, Chao Zuo, Kerry Loomes, Aimin Xu, Liangxue Lai, Xin Liu, Ziyuan Duan, Xiaoyan Hui, Donghai Wu.

Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, the detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis on morphological, histological and molecular features. Principal component analysis (PCA) of differential expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signaling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.

Keywords: MRI; iBAT; immune cells; rabbit; transcriptomic analysis; whitening

DOI: https://doi.org/10.1080/21623945.2022.2111053

Redox Biol. 2022 Aug 18. pii: S2213-2317(22)00219-1. [Epub ahead of print]56 102447

The coupling of mitoproteolysis and oxidative phosphorylation enables tracking of an active mitochondrial state through MitoTimerfluorescence.

Yinyin Xie, Yannan Zhang, Aina Sun, Yamei Peng, Weikang Hou, Cong Xiang, Guoxin Zhang, Beibei Lai, Xiaoshuang Hou, Fangfang Zheng, Fan Wang, Geng Liu.

The regulation of mitochondria function and health is a central node in tissue maintenance, ageing as well as the pathogenesis of various diseases. However, the maintenance of an active mitochondrial functional state and its quality control mechanisms remain incompletely understood. By studying mice with a mitochondria-targeted reporter that shifts its fluorescence from "green" to "red" with time (MitoTimer), we found MitoTimer fluorescence spectrum was heavily dependent on the oxidative metabolic state in the skeletal muscle fibers. The mitoproteolytic activity was enhanced in an energy dependent manner, and accelerated the turnover of MitoTimer protein and respiratory chain substrate, responsible for a green predominant MitoTimer fluorescence spectrum under the oxidative conditions. PGC1α, as well as anti-ageing regents promoted enhanced mitoproteolysis. In addition, cells with the green predominant mitochondria exhibited lower levels of MitoSox and protein carbonylation, indicating a favorable redox state. Thus, we identified MitoTimer as a probe for mitoproteolytic activity in vivo and found a heightened control of mitoproteolysis in the oxidative metabolic state, providing a framework for understanding the maintenance of active oxidative metabolism while limiting oxidative damages.

Keywords: MitoTimer; Mitoproteolysis; Muscle fiber type; Oxidative metabolism; PGC-1α

DOI: https://doi.org/10.1016/j.redox.2022.102447