SUMMARY While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means to induce beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every other day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue, and dramatically ameliorates obesity, insulin resistance and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to the elevation of the fermentation products acetate and lactate, and the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.

Plants have evolved a delicate molecular system to fine-tune their growth and development in response to dynamically changing light environments. In this study, we found that BBX28, a B-box domain protein, negatively regulates photomorphogenic development in a dose-dependent manner in Arabidopsis thaliana. BBX28 interferes with the binding of transcription factor HY5 to the promoters of its target genes through physical interactions, thereby repressing its activity and negatively affecting HY5-regulated gene expression. In darkness, BBX28 associates with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) and undergoes COP1-mediated degradation via the 26S proteasome system. Collectively, these results demonstrate that BBX28 acts as a key factor in the COP1-HY5 regulatory hub by maintaining proper HY5 activity to ensure normal photomorphogenic development in plants.

Light-mediated seedling development is coordinately controlled by a variety of key regulators. Here, we identified two B-box (BBX)-containing proteins, BBX30 and BBX31, as repressors of photomorphogenesis. ELONGATED HYPOCOTYL5, a central regulator of light signaling, directly binds to the G-box cis-element present in the promoters of BBX30 and BBX31 and negatively controls their transcription levels in the light. Seedlings with mutations in BBX30 or BBX31 are hypersensitive to light, whereas the overexpression of BBX30 or BBX31 leads to hypo-photomorphogenic growth in the light. Furthermore, transgenic and phenotypic analysis revealed that the B-box domain of BBX30 or BBX31 is essential for their respective functioning in the regulation of photomorphogenic development in plants. In conclusion, BBX30 and BBX31 act as key negative regulators of light signaling, and their transcription is repressed by ELONGATED HYPOCOTYL5 through directly associating with their promoters.

We applied suppression subtractive hybridization and mirror orientation selection to compare gene expression profiles of isolated Nicotiana tabacum cv SR1 zygotes and egg cells. Our results revealed that many differentially expressed genes in zygotes were transcribed de novo after fertilization. Some of these genes are critical to zygote polarity and pattern formation during early embryogenesis. This suggests that the transcriptome is restructed in zygote and that the maternal-to-zygotic transition happens before the first zygotic division, which is much earlier in higher plants than in animals. The expressed sequence tags used in this study provide a valuable resource for future research on fertilization and early embryogenesis.

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Pharmacist interventions, interacted directly with the physicians at ward level, could play an important role in optimizing antibiotic use, thus lead to the reduction in patients' length of hospital stay and health care cost.

SUMMARYThe maternal-to-zygotic transition (MZT) is characterized by the turnover of zygote development from maternal to zygotic control, and has been extensively studied in animals. A majority of studies have suggested that early embryogenesis is maternally controlled and that the zygotic genome remains transcriptionally inactive prior to the MZT. However, little is known about the MZT in higher plants, and its timing and impact remain uncharacterized. Here, we constructed cDNA libraries from tobacco (Nicotiana tabacum) egg cells, zygotes and two-celled embryos for gene expression profiling analysis, followed by RT-PCR confirmation. These analyses, together with experiments using zygote microculture coupled with transcription inhibition, revealed that a marked change in transcript profiles occurs approximately 50 h after fertilization, and that the MZT is initiated prior to zygotic division in tobacco. Although maternal transcripts deposited in egg cells support several early developmental processes, they appear to be insufficient for zygotic polar growth and subsequent cell divisions. Thus, we propose that de novo transcripts are probably required to trigger embryogenesis in later zygotes in tobacco.

PPARα (PPARA), expressed in most oxidative tissues, is a major regulator of lipid homeostasis; hepatic PPARA plays a critical role during the adaptive fasting response by promoting FA oxidation (FAO). To clarify whether extrahepatic PPARA activity can protect against lipid overload when hepatic PPARA is impaired, lipid accumulation was compared in WT ( ), total body-null ( ), and hepatocyte-specific-null ( ) mice that were fasted for 24 h. Histologic staining indicated reduced lipid accumulation in versus mice, and biochemical analyses revealed diminished medium- and long-chain FA accumulation in mouse livers. Hepatic PPARA target genes were suppressed in both mouse models. Serum FFAs increased in all genotypes after fasting but were highest in mice. In mice, FAO genes were increased in brown adipose tissue, heart, and muscle, and total lipase activity was elevated in the muscle and heart, suggesting increased lipid utilization. Thus, extrahepatic PPARA activity reduces systemic lipid load when hepatic lipid metabolism is impaired by elevating FAO and lipase activity in other tissues and, as a result, protects against fasting-induced hepatosteatosis. This has important clinical implications in disease states with impaired hepatic PPARA function, such as nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.