Unraveling the complexity of thermogenic remodeling of white fat reveals potential antiobesity therapies

Adipose tissue is a complex organ consisting of a mixture of mature adipocytes and stromal vascular cells. It displays a remarkable ability to adapt to environmental and dietary cues by changing its morphology and metabolic capacity. This plasticity is demonstrated by the emergence of interspersed thermogenic beige adipocytes within white depots in response to catecholamines secretion. Coordinated cellular interaction between different cell types within the tissue and a fine-tuned transcriptional program synergistically take place to promote beige remodeling. However, both cell–cell interactions and molecular mechanisms governing beige adipocyte appearance and maintenance are poorly understood. In this and the previous issue of Genes & Development, Shao and colleagues (pp. 1461–1474) and Shan and colleagues (pp. 1333–1338) advance our understanding of these issues and, in doing so, highlight potential therapeutic strategies to combat obesity-associated diseases.

Molecular Plasticity in Animal Pigmentation: Emerging Processes Underlying Color Changes

Synopsis Animal coloration has been rigorously studied and has provided morphological implications for fitness with influences over social behavior, predator–prey interactions, and sexual selection. In vertebrates, its study has developed our understanding across diverse fields ranging from behavior to molecular biology. In the search for underlying molecular mechanisms, many have taken advantage of pedigree-based and genome-wide association screens to reveal the genetic architecture responsible for pattern variation that occurs in early development. However, genetic differences do not provide a full picture of the dynamic changes in coloration that are most prevalent across vertebrates at the molecular level. Changes in coloration that occur in adulthood via phenotypic plasticity rely on various social, visual, and dietary cues independent of genetic variation. Here, I will review the contributions of pigment cell biology to animal color changes and recent studies describing their molecular underpinnings and function. In this regard, conserved epigenetic processes such as DNA methylation play a role in lending plasticity to gene regulation as it relates to chromatophore function. Lastly, I will present African cichlids as emerging models for the study of pigmentation and molecular plasticity for animal color changes. I posit that these processes, in a dialog with environmental stimuli, are important regulators of variation and the selective advantages that accompany a change in coloration for vertebrate animals.

A Molecular Basis for Reciprocal Regulation between Pheromones and Hormones in Response to Dietary Cues in C. elegans

Under stressful conditions, the early larvae of C. elegans enter dauer diapause, a non-aging period, driven by the seemingly opposite influence of ascaroside pheromones (ASCRs) and steroid hormone dafachronic acids (DAs). However, the molecular basis of how these small molecules engage in competitive crosstalk in coordination with insulin/IGF-1 signaling (IIS) remains elusive. Here we report a novel transcriptional regulatory pathway that seems to operate between the ASCR and DA biosynthesis under ad libitum (AL) feeding conditions or bacterial deprivation (BD). Although expression of the ASCR and DA biosynthetic genes reciprocally inhibit each other, ironically and interestingly, such dietary cue-mediated modulation requires the presence of the competitors. Under BD, induction of ASCR biosynthetic gene expression required DA, while ASCR suppresses the expression of the DA biosynthetic gene daf-36. The negative regulation of DA by ASCR was IIS-dependent, whereas daf-36 regulation appeared to be independent of IIS. These observations suggest that the presence of ASCR determines the IIS-dependency of DA gene expression regardless of dietary conditions. Thus, our work defines a molecular basis for a novel reciprocal gene regulation of pheromones and hormones to cope with stressful conditions during development and aging.

Selective phosphorylation of AKT isoforms in response to dietary cues

A calorie-rich diet is one reason for the continuous spread of metabolic syndromes in western societies. Smart food design is one powerful tool to prevent metabolic stress, and the search for suitable bioactive additives is a continuous task. The nutrient-sensing insulin signaling pathway is an evolutionary conserved mechanism that plays an important role in metabolism, growth and development. Recently, lipid cues capable to stimulate insulin signaling were identified. However, the mechanistic base of their activity remains obscure to date. Here, we show that specific AKT/ Protein kinase B isoforms are responsive to dietary lipid extract compositions and potentiate cellular insulin signaling levels. Our data add a new dimension to existing models and position Drosophila as a powerful model to study the relation between dietary lipid cues and the insulin induced cellular signal cascade.

Unpredictable homeodynamic and ambient constraints on irrational decision making of aneural and neural foragers

Foraging for nutritional sustenance represents common significant learned/heritable survival strategies evolved for phylum-diverse cellular life on Earth. Unicellular aneural to multicellular neural foragers display conserved rational or irrational decision making depending on outcome predictions for noise-susceptible real/illusory homeodynamic and ambient dietary cues. Such context-dependent heuristic-guided foraging enables optimal, suboptimal, or fallacious decisions that drive organismal adaptation, health, longevity, and life history.

Diet-based assortative mating through sexual imprinting

Speciation is facilitated when traits subject to divergent selection also contribute to non-random mating—so-called ‘magic traits.’ Diet is a potential magic trait in animal populations because selection for divergence in consumed food may contribute to assortative mating and therefore sexual isolation. However, the mechanisms causing positive diet-based assortment are largely unknown. Here, using diet manipulations in a sexually imprinting species of mouse, Peromyscus gossypinus (the cotton mouse), we tested the hypothesis that sexual imprinting on a divergent diet could be a mechanism that generates rapid and significant sexual isolation. We provided breeding pairs with novel garlic- or orange-flavored water and assessed whether their offspring, exposed to these flavors in utero and in the nest before weaning, later preferred mates that consumed the same flavored water as their parents. While males showed no preference, females preferred males of their parental diet, which generated significant sexual isolation. Thus, our experiment demonstrates that sexual imprinting on dietary cues learned in utero and/or postnatally can facilitate reproductive isolation and potentially speciation.

Predator recognition of chemical cues in crayfish: diet and experience influence the ability to detect predation threats

Aquatic prey often alter their morphology, physiology, and/or behaviour when presented with predatory chemical cues which are heavily influenced by the diet of the predator. We tested the roles that diet and prey familiarity with predators play in the ability of prey to recognize predator threats. Odours from two fish, bass and cichlid fed a vegetarian, protein, heterospecific, and a conspecific diet, were collected and presented to virile crayfish in a choice arena. Our results show that crayfish altered their behaviour in the presence of odours containing conspecific, as opposed to heterospecific diets, but only from familiar predators. A reduced anti-predator response was measured with odours from an unfamiliar predator fed conspecific crayfish. Therefore, crayfish may be able to determine different threat levels based on the different dietary cues from a potential predator, but only when the prey have familiarity with the predators.