Low- and high-thermogenic brown adipocyte subpopulations coexist in murine adipose tissue

Brown adipose tissue (BAT), as the main site of adaptive thermogenesis, exerts beneficial metabolic effects on obesity and insulin resistance. BAT has been previously assumed to contain a homogeneous population of brown adipocytes. Utilizing multiple mouse models capable of genetically labeling different cellular populations, as well as single-cell RNA sequencing and 3D tissue profiling, we discovered a new brown adipocyte subpopulation with low thermogenic activity coexisting with the classical high-thermogenic brown adipocytes within the BAT. Compared with the high-thermogenic brown adipocytes, these low-thermogenic brown adipocytes had substantially lower Ucp1 and Adipoq expression, larger lipid droplets, and lower mitochondrial content. Functional analyses showed that, unlike the high-thermogenic brown adipocytes, the low-thermogenic brown adipocytes have markedly lower basal mitochondrial respiration, and they are specialized in fatty acid uptake. Upon changes in environmental temperature, the 2 brown adipocyte subpopulations underwent dynamic interconversions. Cold exposure converted low-thermogenic brown adipocytes into high-thermogenic cells. A thermoneutral environment had the opposite effect. The recruitment of high-thermogenic brown adipocytes by cold stimulation is not affected by high fat diet feeding, but it does substantially decline with age. Our results revealed a high degree of functional heterogeneity of brown adipocytes

Correction to: Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C

The original article [1] mistakenly omitted a source of funding, and the authors would like to rectify this by acknowledging the additional support of the Natural Science Foundation in Jiangsu Province (BK20150687)

Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels and Neonate Growth in Mice

Breastfeeding offers a broad spectrum of health benefits for infants. However, overnutrition and a steady increase in maternal obesity in the U.S. have made it harder for many mothers to produce and express breastmilk, and the quality of milk from obese mothers is also frequently compromised. Adipocytes, the primary cell type in the non-lactating breast, display a drastic morphological and functional change during lactation in mice. Lipid-filled adipocytes undergo lipolysis, and lipid droplets disappear to provide fatty acids and energy for breastmilk production. Once the animal stops lactation, these lipid-depleted adipocytes return as lipid-laden cells. This dynamic remodeling of the tissue is likely the result of active intercellular communications. Connexin43 (Cx43) is the most abundant connexin in the mammary adipose tissue that makes up the gap junctions for direct intercellular communications. Its expression is increased during lactation and reduced in obese mammary adipose tissue, which is resistant to lactation-induced remodeling. However, whether Cx43 is required for adipocyte remodeling and breastmilk production to support neonates’ growth has not been established. In this study, we used doxycycline-inducible adipocyte-specific Cx43-deleted mice and demonstrated that adipocyte Cx43 played a vital role in determining the carbohydrate levels in breastmilk, which may subsequently affect neonates’ growth

Additional file 4: of Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C

Figure S2. Reprogramming efficiency after palmitoyl-CoA and carnitine treatment in early stage (days 1–7). Relative levels of alkaline phosphatase (AP)-positive colonies with or without palmitoyl-CoA (50 μM) + carnitine (50 μM) treatment after reprogramming. Data are presented as the mean ± SEM (n = 3). ***P < 0.005 (Student’s t test). (TIF 72 kb

PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte

<p>Studies using <i>in vitro</i> cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an <i>in vivo</i> model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1^st meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.</p

Additional file 12: of Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C

Figure S9. Reprogramming efficiency after GSK3β inhibitor treatment in early stage (days 1–3). Relative levels of alkaline phosphatase (AP)-positive colonies with or without GSK3β inhibitor (CHIR99021, 3 μM) after reprogramming. Data are presented as the mean ± SEM (n = 3). ***P < 0.005 (Student’s t test). (TIF 75 kb

Additional file 13: of Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C

Figure S10. Western blot results of the phosphorylation of GSK3β. (a) Western blot for phosphorylation of GSK3β in the reprogramming process with or without CPT1 inhibitors (etomoxir (ETO) or PMS). Repeated Western blot 1. (b) Western blot for phosphorylation of GSK3β in the reprogramming process with or without CPT1 inhibitors (ETO or PMS). Repeated Western blot 2. (TIF 376 kb

Additional file 1: of Fatty acid oxidation promotes reprogramming by enhancing oxidative phosphorylation and inhibiting protein kinase C

Table S1. Primer Sequences. (DOCX 17 kb