As regards feeding the ability to dissipate surplus
As regards feeding, the ability to dissipate surplus energy in the form of heat is beneficial for animals if the protein concentration in the food is low, since it allows them then to meet the adequate protein intake requirement without getting fat. Some of the major dietary activators of the AHR are related to tryptophan, an essential amino acid, and already a partial impairment of global AHR function enhances energy expenditure preventing or mitigating obesity. It is thus conceivable that the AHR's primary function in energy balance might be to secure sufficient protein intake by monitoring the levels of an indicator amino L-Phenylephrine receptor (tryptophan) and, in case of a severe shortage of it threatening protein homeostasis, enable overfeeding of calories without the harmful consequences of substantial overweight such as an impaired ability to escape predators. This scheme is illustrated in Figure 4. (Note that reduced AHR activity as such does not increase food intake.)
Conclusions and future prospects Regarding whole body energy expenditure, the studies expounded here were all conducted in mice. It would therefore be of importance to examine (e.g. with the newly generated AHR knockout rats [31,32]) whether the findings are specific to them or generalizable to other species. Another issue to address in the future concerns further clarification of the tissues that are essential to the augmentation of energy expenditure by global AHR functional impairment. In addition to brown adipose tissue and muscle, the upstream neural regulators of their function (Figure 4) should be subjected to scrutiny. Nervous system-, brown adipose tissue- and striated muscle-specific knockouts should help discern whether the effector or the regulatory tissue is critical in this regard. Finally, a mechanistic key question to address in more detail in the future is the contribution of canonical and non-canonical AHR signaling pathways to obesity. It is clear that these findings have implications also for human health, since obesity or being overweight are currently very common ailments world-wide. In humans, serum AHR ligand concentrations (total TEQs as measured by a cell-based AHR ligand activity assay or HRGC/HRMS) have been reported to be associated with the metabolic syndrome, mitochondrial dysfunction and insulin resistance in Korea [33,34]. Hence, these obesity-related disorders seem to correlate with AHR activity also in humans, and blocking AHR activity by dietary or pharmacological means might offer a novel way to treat them. To that end, it is interesting that resveratrol, a natural AHR antagonist  present in red wine, has been shown to cause brown adipose tissue activation and white fat browning in rodents, albeit at high doses . As global AHR antagonism may result in untoward side effects such as reduced disease tolerance , selective inhibition of AHR function in the tissue(s) responsible for the protection against obesity should be an important aspect of future AHR research.
Acknowledgement This work was supported by a grant from the Academy of Finland (research grant number 261232).
Introduction The amounts of extracellular matrix (ECM) components in the dermis, such as collagen, elastin, proteoglycan, and fibronectin, are regulated by control of the balance between two opposing processes: production and degradation. Transforming growth factor (TGF)-ß is a major profibrotic cytokine that transforms fibroblasts into myofibroblasts, which synthesize ECM proteins . In scleroderma, fibroblasts that have been aberrantly activated through TGF-ß signaling may result in the production of abundant collagen . ECM proteolysis is regulated by matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs) . MMPs, zinc-dependent endopeptidases, are secreted by keratinocyte and dermal fibroblasts in response to various stimuli including UV radiation , , . MMPs degrade various components of ECM proteins and play critical roles in the development of photoaged skin , , .