Abstract:Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the … Show more
“…To further characterize the early active phase exercise response, the regulation of genes showing previous connections to stress- and adrenergic-responsive processes was investigated. Accordingly, genes responsive to stress or glucocorticoid stimuli (such as Nr4a1, Nr4a3, Vegfα, and Adrb2 ) ( 25 – 27 ), as well as genes associated with adipose tissue browning and thermogenesis (such as Cpeb2, Cyp2b10, Pdk4, Slc25a25, Cpeb2, Vegfα, Pgc1α, Ucp1, Dio2, Gadd45g, Irf4, Zfp516, and Crem ) ( 28 – 37 ), were uniquely up-regulated by exercise at the early active phase ( Fig. 2 F ).…”
The circadian clock is a cell-autonomous transcription–translation feedback mechanism that anticipates and adapts physiology and behavior to different phases of the day. A variety of factors including hormones, temperature, food-intake, and exercise can act on tissue-specific peripheral clocks to alter the expression of genes that influence metabolism, all in a time-of-day dependent manner. The aim of this study was to elucidate the effects of exercise timing on adipose tissue metabolism. We performed RNA sequencing on inguinal adipose tissue of mice immediately following maximal exercise or sham treatment at the early rest or early active phase. Only during the early active phase did exercise elicit an immediate increase in serum nonesterified fatty acids. Furthermore, early active phase exercise increased expression of markers of thermogenesis and mitochondrial proliferation in inguinal adipose tissue. In vitro, synchronized 3T3-L1 adipocytes showed a timing-dependent difference in
Adrb2
expression, as well as a greater lipolytic activity. Thus, the response of adipose tissue to exercise is time-of-day sensitive and may be partly driven by the circadian clock. To determine the influence of feeding state on the time-of-day response to exercise, we replicated the experiment in 10-h-fasted early rest phase mice to mimic the early active phase metabolic status. A 10-h fast led to a similar lipolytic response as observed after active phase exercise but did not replicate the transcriptomic response, suggesting that the observed changes in gene expression are not driven by feeding status. In conclusion, acute exercise elicits timing-specific effects on adipose tissue to maintain metabolic homeostasis.
“…To further characterize the early active phase exercise response, the regulation of genes showing previous connections to stress- and adrenergic-responsive processes was investigated. Accordingly, genes responsive to stress or glucocorticoid stimuli (such as Nr4a1, Nr4a3, Vegfα, and Adrb2 ) ( 25 – 27 ), as well as genes associated with adipose tissue browning and thermogenesis (such as Cpeb2, Cyp2b10, Pdk4, Slc25a25, Cpeb2, Vegfα, Pgc1α, Ucp1, Dio2, Gadd45g, Irf4, Zfp516, and Crem ) ( 28 – 37 ), were uniquely up-regulated by exercise at the early active phase ( Fig. 2 F ).…”
The circadian clock is a cell-autonomous transcription–translation feedback mechanism that anticipates and adapts physiology and behavior to different phases of the day. A variety of factors including hormones, temperature, food-intake, and exercise can act on tissue-specific peripheral clocks to alter the expression of genes that influence metabolism, all in a time-of-day dependent manner. The aim of this study was to elucidate the effects of exercise timing on adipose tissue metabolism. We performed RNA sequencing on inguinal adipose tissue of mice immediately following maximal exercise or sham treatment at the early rest or early active phase. Only during the early active phase did exercise elicit an immediate increase in serum nonesterified fatty acids. Furthermore, early active phase exercise increased expression of markers of thermogenesis and mitochondrial proliferation in inguinal adipose tissue. In vitro, synchronized 3T3-L1 adipocytes showed a timing-dependent difference in
Adrb2
expression, as well as a greater lipolytic activity. Thus, the response of adipose tissue to exercise is time-of-day sensitive and may be partly driven by the circadian clock. To determine the influence of feeding state on the time-of-day response to exercise, we replicated the experiment in 10-h-fasted early rest phase mice to mimic the early active phase metabolic status. A 10-h fast led to a similar lipolytic response as observed after active phase exercise but did not replicate the transcriptomic response, suggesting that the observed changes in gene expression are not driven by feeding status. In conclusion, acute exercise elicits timing-specific effects on adipose tissue to maintain metabolic homeostasis.
“…Another study showed that the deficiency of Hspa12a, member of the Hsp70 family, promoted greater browning in iWAT of knockout mice compared to wild type during cold exposure and suggested this effect could be mediated through paracrine mechanisms (Cheng et al, 2019). In contrast to the above, Kim et al found that Hsph1, Hsp90aa1, and Hspa8 are upregulated in BAT of young and old mice exposed to acute cold exposure (Kim et al, 2021). In the current study, the expression of Hspa1a and Hspa1b were lower in iWAT compared to BAT and β3adrenergic stimulation through CL further decreased their expression.…”
Activation of thermogenic adipose tissue depots has been linked to improved metabolism and weight loss. To study the molecular regulation of adipocyte thermogenesis, we performed RNA‐Seq on brown adipose tissue (BAT), gonadal white adipose tissue (gWAT), and inguinal white adipose tissue (iWAT) from mice treated with β3‐adrenoreceptor agonist CL316,243 (CL). Our analysis revealed diverse transcriptional profile and identified pathways in response to CL treatment. Differentially expressed genes (DEGs) in iWATCL were associated with the upregulation of pathways involved in cellular immune responses and with the upregulation of the browning program. We identified 39 DEGs in beige adipose which included certain heat shock proteins (Hspa1a and Hspa1b), and others suggesting potential associations with browning. Our results highlight transcriptional heterogeneity across adipose tissues and reveal genes specifically regulated in beige adipose, potentially aiding in identifying novel browning pathways.
“…RNA sequencing with next-generation sequencing technology has provided a powerful, highly reproducible, and cost-effective tool (Xu et al, 2018). In recent years, transcriptome studies have reported specific molecular mechanisms and candidate genes for cold-exposed humans (Kim et al, 2021), mice (Shore et al, 2013), fish (Xu et al, 2018;Sun et al, 2019;Liu et al, 2020), gray treefrog (Amaral et al, 2020), and shrimp (Zhuo et al, 2020). In the current study, we focused on skeletal muscle, as both ST and NST could contribute to systemic thermoregulation (Fuller-Jackson and Henry, 2018;Roesler and Kazak, 2020;Grigg et al, 2022).…”
Cold tolerance is an important trait for sheep raised at high altitudes. Muscle tissue, comprising 30–40% of the total body mass, produces heat during cold exposure. However, little is known about the genetic mechanisms of this tissue and its role in thermogenesis in lambs. We examined genes in skeletal muscle tissue in a cold-adapted sheep breed, Altay, and a cold-intolerant sheep breed, Hu, when exposed to low air temperature. Three ewe-lambs of each breed were maintained at −5°C and three ewe-lambs of each breed were maintained at 20°C. After cold exposure for 25 days, the longissimus dorsi of each lamb was collected, and transcriptome profiles were sequenced and analyzed. The results of RNA-seq showed that the average reads among the four groups were 11.0 Gbase. The genome mapping rate averaged 88.1% and the gene mapping rate averaged 82.5%. The analysis of differentially expressed genes (DEGs) indicated that the peroxisome proliferator-activated receptors (PPAR), cAMP, and calcium signaling pathways and muscle contraction in muscle tissue were linked to thermogenesis in cold-exposed lambs. Furthermore, PCK1 (phosphoenolpyruvate carboxykinase1) increased glyceroneogenesis in cold-exposed Altay lambs, and APOC3 (apolipoprotein C3), LPL (lipoprotein lipase), and FABP4 (fatty acid binding protein 4, adipocyte) were involved in the intake and transport of free fatty acids. In Hu sheep, cAMP biosynthesis from ATP hydrolysis was regulated by ADCY10 (adenylate cyclase) and ADORA2a (adenosine A2a receptor). Skeletal muscle contraction was regulated by MYL2 (myosin light chain 2). In conclusion, cold exposure altered the expression level of genes involved in heat production in muscle tissue. Some potential mechanisms were revealed, including calcium ion transport in the calcium signaling pathway, fatty acid metabolism in the PPAR signaling pathway, and cAMP biosynthesis in the cAMP signaling pathway. This study implied that skeletal muscle plays an important role in thermoregulation in lambs.
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