Despite tremendous research efforts to identify regulatory factors that control energy metabolism, the prevalence of obesity has been continuously rising, with nearly 40% of US adults being obese. Interactions between secretory factors from adipose tissues and the nervous system innervating adipose tissues play key roles in maintaining energy metabolism and promoting survival in response to metabolic challenges. It is currently accepted that there are three types of adipose tissues, white (WAT), brown (BAT), and beige (BeAT), all of which play essential roles in maintaining energy homeostasis. WAT mainly stores energy under positive energy balance, while it releases fuels under negative energy balance. Thermogenic BAT and BeAT dissipate energy as heat under cold exposure to maintain body temperature. Adipose tissues require neural and endocrine communication with the brain. A number of WAT adipokines and BAT batokines interact with the neural circuits extending from the brain to cooperatively regulate whole-body lipid metabolism and energy homeostasis. We review neuroanatomical, histological, genetic, and pharmacological studies in neuroendocrine regulation of adipose function, including lipid storage and mobilization of WAT, non-shivering thermogenesis of BAT, and browning of BeAT. Recent whole-tissue imaging and transcriptome analysis of differential gene expression in WAT and BAT yield promising findings to better understand the interaction between secretory factors and neural circuits, which represents a novel opportunity to tackle obesity.

Consumption of a high-fat diet (HFD) promotes the development of obesity, a disease resulting from an imbalance between energy intake and energy expenditure. Brown adipose tissue (BAT) has thermogenic capacity that burns calories to produce heat, and it is a potential target for the treatment and prevention of obesity. There is limited information regarding the impact of HFD on the BAT transcriptome. We hypothesized that HFD-induced obesity would lead to transcriptional regulation of BAT genes. RNA sequencing was used to generate global transcriptome profiles from BAT of lean mice fed with a low-fat diet (LFD) and obese mice fed with a HFD. Gene Ontology (GO) analysis identified increased expression of genes involved in biological processes (BP) related to immune responses, which enhanced molecular function (MF) in chemokine activity; decreased expression of genes involved in BP related to ion transport and muscle structure development, which reduced MF in channel and transporter activity and structural binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathway analysis indicated that pathways associated with innate immunity were enhanced by HFD, while pathways associated with muscle contraction and calcium signaling were suppressed by HFD. Collectively, these results suggest that diet-induced obesity changes transcriptomic signatures of BAT, leading to dysfunction involving inflammation, calcium signaling, ion transport, and cell structural development.

Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear. In this study, female and male adolescent Sprague Dawley rats received one-hour restraint stress daily from postnatal day (PD) 32 to PD44. Corticosterone levels, body weights, food intake, body composition, and circulating adiposity and sex hormones were measured. On PD44, brain and blood samples were collected. Using RNA-sequencing, sex-specific differences in stress-induced differentially expressed (DE) genes were identified in subregions of the hypothalamus, limbic system, and prefrontal cortex. Canonical pathways reflected well-known sex-distinct maladies and diseases, substantiating the therapeutic potential of the DE genes found in the current study. Thus, we proposed specific sex distinct, adolescent stress-induced transcriptional changes found in the current study as examples of the molecular bases for sex differences witnessed in stress induced or exacerbated emotional and metabolic disorders. Future behavioral studies and single-cell studies are warranted to test the implications of the DE genes identified in this study in sex-distinct stress-induced susceptibilities.