- Hormones, Metabolism and the Benefits of Exercise: Human Brown Adipose Tissue Plasticity: Hormonal and Environmental Manipulation [BOOK]
- BOOKSpringer: Chamcham
- Brown adipose tissue (BAT), brown-in-white (“brite”) and “beige” adipocytes share the unique ability of converting chemical energy into heat and play a critical role in the adaptive thermogenesis res…
Brown adipose tissue (BAT), brown-in-white (“brite”) and “beige” adipocytes share the unique ability of converting chemical energy into heat and play a critical role in the adaptive thermogenesis response promoting nonshivering thermogenesis. Uncoupling Protein-1 (UCP1), which allows the uncoupling of substrate oxidation from phosphorylation of ADP, represents the molecular signature of BAT and beige adipocytes. Until recently, the physiologic role of BAT and beige adipocytes depots was thought to be limited to small mammalians and newborns. The discovery of BAT in adult humans and the demonstration of the presence of inducible BAT activity in white adipose tissue by beige adipocytes have generated enthusiasm as potential targets for treatment of obesity and other disorders due to sustained positive energy balance. These findings are particularly important since in vitro studies have demonstrated that preadipocytes can be directed toward a common brown phenotype by multiple pathways that, in turn, may be exploited for therapeutic interventions. In adult humans, BAT activity is more evident in deep neck fat depots and, to a lesser degree, in subcutaneous adipose tissue, with a transcriptome signature resembling the rodent beige fat. This observation supports the hypothesis that human BAT activity and capacity can be modulated. To this end, we have directed our translational research program toward the characterization of beige fat in humans and on the effects of hormonal and environmental drivers in the adaptive thermogenesis response. Mild cold exposure, within the temperature range commonly employed in climate-controlled buildings, is sufficient to generate a significant increase in non-shivering thermogenesis driven by BAT and beige adipocyte activation. In turn, adaptive thermogenesis generates a specific hormonal signature and promotes glucose disposal. Chronic exposure to mild cold induces expansion of BAT mass and activity, whereas exposure to warm climate abrogates them. Additionally, the metabolic effects of BAT mass expansion are evident only upon stimulation of BAT activity, indicating that both expansion and activation of BAT are necessary and complementary strategies to pursue. From an experimental standpoint, human preadipocytes represent a viable experimental platform to mechanistically interrogate different pathways that are able to expand and activate browning. Our laboratory has focused on studying FGF-21, and FNDC5/irisin in their capacity to promote the browning process. Compared to a white differentiation medium, the addition of either FGF-21 or FNDC5 results in a reprogramming toward a brown phenotype, as indicated by the display of brown transcriptome signature and, functionally, by the increase in oxygen consumption following catecholamine treatment, indicating an increase in substrate utilization. Collectively, the integration of a detailed assessment of human physiology with mechanistic observations in cell culture systems can provide a unique opportunity to translate observations from experimental models to actionable therapeutic targets.
- Fingerprinting a Living Cell by Raman Integrated Mid-Infrared Photothermal Microscopy. [Journal Article]
- ACAnal Chem 2019 Jul 17
- Vibrational spectroscopic imaging techniques, based on infrared absorption or Raman scattering, allow for noninvasive chemically specific visualization of biological systems. The infrared and Raman m…
Vibrational spectroscopic imaging techniques, based on infrared absorption or Raman scattering, allow for noninvasive chemically specific visualization of biological systems. The infrared and Raman modalities with different selection rules provide complementary information. Specifically, infrared microscopy provides strong signals in the fingerprint region but suffers from low spatial resolution. Raman microscopy provides sub-micrometer resolution but requires a long acquisition time. We developed a system that combines the strengths of both techniques by integrating confocal Raman microspectroscopy to the recently developed mid-infrared photothermal microscopy. This hybrid system is capable of fast infrared photothermal imaging of living cells with sub-micrometer resolution to identify points of interest, followed by a full-spectrum Raman analysis of the identified objects. In addition, a fingerprint photothermal spectrum can be acquired by scanning the wavelengths of the infrared laser. Comprehensive vibrational fingerprint mapping of living cells, demonstrated in adipocytes and single bacteria, promises broad applications of this technology in biology and material science.
- Modified apple polysaccharide regulates microbial dysbiosis to suppress high-fat diet-induced obesity in C57BL/6J mice. [Journal Article]
- EJEur J Nutr 2019 Jul 16
- CONCLUSIONS: MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.
- Pathogenic Effects and Potential Regulatory Mechanisms of Tea Polyphenols on Obesity. [Journal Article]
- BRBiomed Res Int 2019; 2019:2579734
- Overweight and obesity are major threats to human health. Tea polyphenols exert multiple beneficial effects on human health and may play a positive regulatory role in fat assumption. However, how tea…
Overweight and obesity are major threats to human health. Tea polyphenols exert multiple beneficial effects on human health and may play a positive regulatory role in fat assumption. However, how tea polyphenols contribute to the regulation of fat metabolism remains unclear to date. Small RNA expression profile can be regulated by tea polyphenols in adipocytes. Therefore, tea polyphenols may regulate fat metabolism by controlling small RNA-associated biological processes. In this study, we developed a systematic research platform based on mouse models and performed small RNA sequencing to identify the specific role of small RNAs in the regulatory effect of tea polyphenols on fat metabolism. We compared the expression levels of different small RNA subtypes, including piRNAs and miRNAs, and identified a group of differentially expressed small RNAs in the experimental and control groups. Most of these small RNAs participate in lipid metabolism, suggesting that small RNAs play a significant role in tea polyphenol-associated obesity and related pathogenesis. Furthermore, gene ontology and KEGG pathway enrichment indicated that small RNAs influence the regulatory effects of tea polyphenols on obesity, revealing the potential pathogenic mechanisms for such nutritional disease.
- PRDM16 Represses the Pig White Lipogenesis through Promoting Lipolysis Activity. [Journal Article]
- BRBiomed Res Int 2019; 2019:1969413
- The positive regulatory domain containing 16 (PRDM16) gene is a dominant transcriptional regulator that favors the "browning" of white adipocytes in rodents. Since the "browning" of white fat is impo…
The positive regulatory domain containing 16 (PRDM16) gene is a dominant transcriptional regulator that favors the "browning" of white adipocytes in rodents. Since the "browning" of white fat is important in pig in terms of producing heat fighting against cold environment, avoiding obesity, and improving meat quality, understanding the critical role that PRDM16 gene played in pig adipose "browning" and energy metabolism is of great significance. However, the constitution of pig fat differs a lot from rodents and human as they do not have brown adipose tissue (BAT) even in the newborn piglets. In this study, we isolated porcine primary preadipocytes and investigated the function of PRDM16 during preadipocytes differentiation. Our results showed that overexpression of the PR domain of PRDM16 repressed the differentiation of porcine preadipocytes, indicated by oil red O staining and the deposition of the triglyceride. Overexpression of the PR domain significantly increased the level of lipolysis and mitochondrial oxidative capacity detected by Western blotting during differentiation. Furthermore, we purified the protein coded by the PR domain and demonstrated that this protein has the H3K9me1 methyltransferase activity. In conclusion, the PR domain of the porcine PRDM16 gene repressed the mature of the porcine preadipocytes by promoting its oxidative activity.
- MSC: immunoregulatory effects, roles on neutrophils and evolving clinical potentials. [Journal Article]
- AJAm J Transl Res 2019; 11(6):3890-3904
- Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic stem cells capable of differentiating into varieties of mature cell types such as osteoblasts, chondrocytes, adipocytes, and myoblasts…
Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic stem cells capable of differentiating into varieties of mature cell types such as osteoblasts, chondrocytes, adipocytes, and myoblasts. MSCs can be isolated from different kinds of tissues and cultivated in vitro for amplification and passage easily. These cells have drawn researcher's attention lately due to their ability of tissue repair, properties of hematopoiesis support and function of immunoregulation through the secretion of a variety of cytokines and growth factors that have both paracrine and autocrine activities. MSCs can regulate the proliferation of T cells, the antibodies secretion of B cells, maturation of DC, polarization of macrophages and also have many effects on neutrophils such as the suppression of NO secretion, inhibition of apoptosis, reduction of their infiltration, decreasing of N-Formy l-L-Methionine-L-leucy l-L-phenylalanine, induction of respiratory bursts and promotion of survivals. In some conditions, MSCs exert their function of treatment through immunoregulation. We reviewed the multifaceted roles of MSCs in communicating with immune cells mainly neutrophils in both in vivo and in vitro experiments. MSCs may provide promising trends for cell therapy in future.
- Ccr7 null mice are protected against diet-induced obesity via Ucp1 upregulation and enhanced energy expenditure. [Journal Article]
- NMNutr Metab (Lond) 2019; 16:43
- CONCLUSIONS: In Ccr7 null mice, browning of white adipocytes as well as the activation of brown adipocytes cause enhanced energy metabolism, resulting in protection against diet-induced obesity.
- Differentiation Capacity of Human Mesenchymal Stem Cells into Keratocyte Lineage. [Journal Article]
- IOInvest Ophthalmol Vis Sci 2019 Jul 01; 60(8):3013-3023
- CONCLUSIONS: Based on our findings, CSSCs appeared to have the greatest differentiation potential toward the keratocyte lineage and the greatest anti-inflammatory properties in vitro.
- SREBP-regulated adipocyte lipogenesis is dependent on substrate availability and redox modulation of mTORC1. [Journal Article]
- JIJCI Insight 2019 Jul 16; 5
- The synthesis of lipid and sterol species through de novo lipogenesis (DNL) is regulated by two functionally overlapping but distinct transcription factors: the sterol regulatory element-binding prot…
The synthesis of lipid and sterol species through de novo lipogenesis (DNL) is regulated by two functionally overlapping but distinct transcription factors: the sterol regulatory element-binding proteins (SREBPs) and carbohydrate response element binding protein (ChREBP). ChREBP is considered to be the dominant regulator of DNL in adipose tissue (AT); however, the SREBPs are highly expressed and robustly regulated in adipocytes, suggesting that the model of AT DNL may be incomplete. Here we describe a new mouse model of inducible, adipocyte-specific overexpression of the insulin-induced gene 1 (Insig1), a negative regulator of SREBP transcriptional activity. Contrary to convention, Insig1 overexpression did block AT lipogenic gene expression. However, this was immediately met with a compensatory mechanism triggered by redox activation of mTORC1 to restore SREBP1 DNL gene expression. Thus, we demonstrate that SREBP1 activity sustains adipocyte lipogenesis, a conclusion that has been elusive due to the constitutive nature of current mouse models.
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- Antioxidants protect against diabetes by improving glucose homeostasis in mouse models of inducible insulin resistance and obesity. [Journal Article]
- DDiabetologia 2019 Jul 15
- CONCLUSIONS: We conclude that fat mass reduction through insulin resistance in adipocytes is not reversible. Furthermore, it seems unlikely that adipocytes undergo apoptosis during the process of extreme lipolysis, as a consequence of insulin resistance. Antioxidants have a beneficial health effect not only during the acute phase of diabetes development, but also in a temporary fashion once chronic obesity and diabetes have been established.