Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute ...activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX – XXX, 2020)
Graphical Abstract
Graphical Abstract
Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereby increasing energy expenditure. In addition to ...classical brown adipocytes, adult rodents-like adult humans-harbour brown-like adipocytes in the predominantly white adipose tissue. The formation of these brite (brown-in-white) adipocytes is a physiological response to chronic cold and their cellular origin is under debate. We show here that cold-induced formation of brite adipocytes in mice is reversed within 5 weeks of warm adaptation, but the brite adipocytes formed by cold stimulation are not eliminated. Genetic tracing and transcriptional characterization of isolated adipocytes demonstrates that they are converted into cells with the morphology and gene expression pattern of white adipocytes. Moreover, these white-typical adipocytes can convert into brite adipocytes on additional cold stimulation. Shifting the balance of this interconversion from the white towards the brite phenotype might provide a new means of counteracting obesity by increasing energy expenditure.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
3.
Fueling the fire of adipose thermogenesis Wolfrum, Christian; Gerhart-Hines, Zachary
Science (American Association for the Advancement of Science),
2022-Mar-18, 2022-03-18, 20220318, Letnik:
375, Številka:
6586
Journal Article
Recenzirano
Specialized fat tissue generates heat and holds the potential to counter metabolic diseases.
...although DGAT1 loss-of-function in humans causes severe diarrhea-like symptoms (Haas et al, 2012), Dgat1 knockout mice are healthy and resistant to diet-induced obesity (Chen et al, 2002). In ...HFD-fed mice housed at room temperature, D1 + 2i caused > 50% reduction in the plasma FAs at a 4-h timepoint while plasma glycerol and glucose levels were minimally affected (Fig 1C). (B) Indirect calorimetry data shows a reduced respiratory exchange ratio (RER) after D1 + 2i treatment compared to the vehicle-treated group at room temperature (upper panel), or in cold (middle panel). (D) Seahorse extracellular flux analysis to measure the effect of D1 + 2i on the oxygen consumption rate (OCR) as a readout of cellular FAO (Sharma et al, 2023).
Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in ...response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time. Elevated oxidative stress is also found in metabolic diseases such as obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of the energy homeostasis is also associated with aging, and many age-related genes also control energy metabolism, with the adipose organ, comprising white, brite, and brown adipocytes, as an important metabolic player in the regulation of whole-body energy homeostasis. This review summarizes transformations in the adipose organ upon aging and cellular senescence and sheds light on the reallocation of fat mass between adipose depots, on the metabolism of white and brown adipose tissue, on the regenerative potential and adipogenic differentiation capacity of preadipocytes, and on alterations in mitochondria and bioenergetics. In conclusion, the aging process is a lifelong, creeping process with gradual decline in (pre-)adipocyte function over time. Thus, slowing down the accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent preadipocytes as well as blocking deleterious compounds of the senescent secretome are protective measures to maintain a lasting state of health at old age.
There is a growing body of evidence linking maternal overnutrition to obesity and psychopathology that can be conserved across multiple generations. Recently, we demonstrated in a maternal high-fat ...diet (HFD; MHFD) mouse model that MHFD induced enhanced hedonic behaviors and obesogenic phenotypes that were conserved across three generations via the paternal lineage, which was independent of sperm methylome changes. Here, we show that sperm tRNA-derived small RNAs (tsRNAs) partly contribute to the transmission of such phenotypes. We observe increased expression of sperm tsRNAs in the F1 male offspring born to HFD-exposed dams. Microinjection of sperm tsRNAs from the F1-HFD male into normal zygotes reproduces obesogenic phenotypes and addictive-like behaviors, such as increased preference of palatable foods and enhanced sensitivity to drugs of abuse in the resultant offspring. The expression of several of the differentially expressed sperm tsRNAs predicted targets such as CHRNA2 and GRIN3A, which have been implicated in addiction pathology, are altered in the mesolimbic reward brain regions of the F1-HFD father and the resultant HFD-tsRNA offspring. Together, our findings demonstrate that sperm tsRNA is a potential vector that contributes to the transmission of MHFD-induced addictive-like behaviors and obesogenic phenotypes across generations, thereby emphasizing its role in diverse pathological outcomes.
Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 ...reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.
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•Endothelial loss of pfkfb3 impairs ischemic muscle revascularization and regeneration•EC-derived lactate instructs MCT1-dependent macrophage functional polarization•Lactate-polarized macrophages promote muscle revascularization and regeneration•Restoring lactate levels improves macrophage polarization and recovery from ischemia
Endothelial cells (ECs) critically control muscle recovery from ischemia by secreting lactate. Angiocrine lactate is taken up and oxidized by macrophages in an MCT1-dependent fashion. Lactate-mediated macrophage polarization promotes revascularization and muscle regeneration. Consequently, EC-specific loss of pfkfb3 lowers muscle lactate levels and impairs muscle recovery from ischemia.
White adipose tissue stores energy while brown adipose tissue contributes to body temperature maintenance through non-shivering thermogenesis. In addition, brite (brown-in-white) adipocytes ...resembling classical brown adipocytes within predominantly white adipose tissue can be found in response to cold adaptation or other stimuli. Even though our understanding of brite adipocyte formation has increased substantially in the last few years, it is still unclear how brite and classical brown adipocytes are formed in vivo. In this review, we outline and discuss the current understanding of brite adipocyte nomenclature, developmental origin and possible mechanisms of their recruitment. We reason that future work in the field will bridge in vivo tracing studies and primary cell characterization with molecular mechanistic data from in vitro approaches to devise new means to increase energy expenditure.
Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth ...factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus-mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2-dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.
► Maternal-high fat diet leads to enhanced anxiety-like behaviors in the offspring. ► Maternal HFD does not affect conditioned fear response in the offspring. ► Maternal HFD leads to dorsal ...hippocampal BDNF alterations in the offspring. ► Maternal HFD leads to ventral hippocampal serotonergic alterations in the offspring. ► Maternal HFD leads to ventral hippocampal GABAergic alterations in the offspring.
The maternal environment has a significant role in the normal development of the fetus and may have long-term impact on brain development including critical central pathways such as the gamma-aminobutyric acid (GABA), serotonergic and the neurotrophin systems. For example, maternal malnutrition plays an important role in programming many aspects of physiology and behavior including predisposition to mental-health related disorders such as anxiety. Here we investigated the effects of maternal high-fat diet or control diet for nine weeks (prior to gestation, gestation and lactation) on the adult offspring with respect to anxiety related behaviors as well as exploration and conditioned fear response. We found that offspring born to high-fat diet mothers showed increased anxiety-like behaviors, but intact conditioned fear response and exploratory behavior. In addition, brain-derived neurotrophic factor (BDNF) was significantly increased in the dorsal hippocampus, while GABAA alpha2 receptor subunit and 5-hydroxytryptamine 1A (5-HT1A) receptor showed increased levels in the ventral hippocampus. In summary, these findings suggest that maternal high-fat diet consumption during critical periods in the development of the fetus, might increase the risk of abnormal behaviors in adulthood related to anxiety.
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