Adipose tissue is a major site of energy storage and plays a role in regulation of metabolism through release of adipokines. Here we show that mice with a fat-specific knockout of the miRNA-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, have major decreases in circulating exosomal miRNAs. Transplantation of white and especially brown adipose tissue (BAT) into ADicerKO mice restores circulating miRNAs associated with an improvement in glucose tolerance and a reduction of hepatic FGF21 mRNA and circulating FGF21. This gene regulation can be mimicked by administration of normal, but not AdicerKO, serum exosomes. Expression of a human-specific miRNA in BAT of one mouse in vivo can also regulate its 3’UTR-reporter in liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes a major source of circulating exosomal miRNAs, and these miRNAs can regulate gene expression in distant tissues thereby serving as novel forms of adipokines.

We use very deep near-infrared (NIR) imaging data obtained in MOIRCS Deep Survey (MODS) to investigate the evolution of the galaxy stellar mass function back to z ∼ 3. The MODS data reach J = 24.2, H = 23.1, K = 23.1 (5σ, Vega magnitude) over 103 arcmin 2 (wide) and J = 25.1, H = 23.7, K = 24.1 over 28 arcmin 2 (deep) in the GOODS-North region. The wide and very deep NIR data allow us to measure the number density of galaxies down to low stellar mass (10 9 -10 10 M ⊙ ) even at high redshift with high statistical accuracy. The normalization of the mass function decreases with redshift and the integrated stellar mass density becomes ∼ 8-18% of the local value at z ∼ 2 and ∼ 4-9% at z ∼ 3, which are consistent with results of previous studies in general fields. Furthermore, we found that the low-mass slope becomes steeper with redshift from α ∼ −1.3 at z ∼ 1 to α ∼ −1.6 at z ∼ 3, and that the evolution of the number density of low-mass (10 9 -10 10 M ⊙ ) galaxies is weaker than that of M * (∼10 11 M ⊙ ) galaxies. This indicates that the contribution of low-mass galaxies to the total stellar mass density has been significant at high redshift. The steepening of the low-mass slope with redshift is opposite trend expected from the stellar mass dependence of the specific star formation rate reported in previous studies. The present result suggests that the hierarchical merging process overwhelmed the effect of the stellar mass growth by star formation and was very important for the stellar mass assembly of these galaxies at 1 z 3.

Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states.