The Indian Ocean Dipole and El Niño Southern Oscillation as major drivers of coral cover on shallow reefs in the Andaman Sea.

Shallow reefs are a major feature of coral assemblages in the Andaman Sea. At Phuket, Thailand sheltered reefs are dominated by massive corals, together with an increasing abundance of branching species during favourable growth conditions. The growth of coral on these reefs is moderated by long-term increases in sea temperature and relative sea level but fluctuating decadal/intradecadal climate processes of El Niño Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD), which modulate sea level and temperature, are the main drivers of coral cover. In this study, the contribution of these two climate processes was identified and also quantified. Over a 34-year study of fluctuating coral cover, the three major reductions in cover in 1997, 2010 and 2019 were linked to overlapping positive IOD (pIOD) and El Niños in 1997 and 2019, and with an El Niño alone in 2010. Combined pIOD and El Niño depressed sea level was the major factor in reducing cover in 1997 while El Niño extreme sea temperatures were responsible for large reductions in 2010. In 2019, a bi-phasic pIOD and El Niño resulted in lowered cover at a time of both decreased sea level and high sea temperature. Under global warming scenarios, it is projected that extreme pIODs, such as those seen in 1997 and 2019, will occur more frequently while El Niño frequencies will continue to increase even after global mean temperature stabilization. In these circumstances, and with steadily rising background sea temperatures, the future risks to the shallow reefs of the Andaman Sea are substantial, despite any temporary respite gained from climate related or land subsidence sea-level rise. Such findings have wider implications for all reefs affected by climatic-driven sea-level depressions, particularly those around Indonesian shores where similar El-Niño-related reductions in coral cover have been reported.

Coral bleaching.

Tracy Ainsworth and Barbara Brown introduce the causes and consequences of coral bleaching.

Do reef corals age?

Hydra is emerging as a model organism for studies of ageing in early metazoan animals, but reef corals offer an equally ancient evolutionary perspective as well as several advantages, not least being the hard exoskeleton which provides a rich fossil record as well as a record of growth and means of ageing of individual coral polyps. Reef corals are also widely regarded as potentially immortal at the level of the asexual lineage and are assumed not to undergo an intrinsic ageing process. However, putative molecular indicators of ageing have recently been detected in reef corals. While many of the large massive coral species attain considerable ages (>600 years) there are other much shorter-lived species where older members of some populations show catastrophic mortality, compared to juveniles, under environmental stress. Other studies suggestive of ageing include those demonstrating decreased reproduction, increased susceptibility to oxidative stress and disease, reduced regeneration potential and declining growth rate in mature colonies. This review aims to promote interest and research in reef coral ageing, both as a useful model for the early evolution of ageing and as a factor in studies of ecological impacts on reef systems in light of the enhanced effects of environmental stress on ageing in other organisms.

Age-Related Shifts in Bacterial Diversity in a Reef Coral.

This study investigated the relationship between microbial communities in differently sized colonies of the massive coral Coelastrea aspera at Phuket, Thailand where colony size could be used as a proxy for age. Results indicated significant differences between the bacterial diversity (ANOSIM, R = 0.76, p = 0.001) of differently sized colonies from the same intertidal reef habitat. Juvenile and small colonies (< 6 cm mean diam) harboured a lower bacterial richness than medium (~ 10 cm mean diam) and large colonies (> 28 cm mean diam). Bacterial diversity increased in a step-wise pattern from juveniles < small < medium colonies, which was then followed by a slight decrease in the two largest size classes. These changes appear to resemble a successional process which occurs over time, similar to that observed in the ageing human gut. Furthermore, the dominant bacterial ribotypes present in the tissues of medium and large sized colonies of C. aspera, (such as Halomicronema, an Oscillospira and an unidentified cyanobacterium) were also the dominant ribotypes found within the endolithic algal band of the coral skeleton; a result providing some support for the hypothesis that the endolithic algae of corals may directly influence the bacterial community present in coral tissues.

Warm-water coral reefs and climate change.

Coral reefs are highly dynamic ecosystems that are regularly exposed to natural perturbations. Human activities have increased the range, intensity, and frequency of disturbance to reefs. Threats such as overfishing and pollution are being compounded by climate change, notably warming and ocean acidification. Elevated temperatures are driving increasingly frequent bleaching events that can lead to the loss of both coral cover and reef structural complexity. There remains considerable variability in the distribution of threats and in the ability of reefs to survive or recover from such disturbances. Without significant emissions reductions, however, the future of coral reefs is increasingly bleak.

Regional decline in growth rates of massive Porites corals in Southeast Asia.

This study reports the first well-replicated analysis of continuous coral growth records from warmer water reefs (mean annual sea surface temperatures (SST) >28.5 °C) around the Thai-Malay Peninsula in Southeast Asia. Based on analyses of 70 colonies sampled from 15 reefs within six locations, region-wide declines in coral calcification rate (ca. 18.6%), linear extension rate (ca. 15.4%) and skeletal bulk density (ca. 3.9%) were observed over a 31-year period from 1980 to 2010. Decreases in calcification and linear extension rates were observed at five of the six locations and ranged from ca. 17.2-21.6% and ca. 11.4-19.6%, respectively, whereas decline in skeletal bulk density was a consequence of significant reductions at only two locations (ca. 6.9% and 10.7%). A significant link between region-wide growth rates and average annual SST was found, and Porites spp. demonstrated a high thermal threshold of ca. 29.4 °C before calcification rates declined. Responses at individual locations within the region were more variable with links between SST and calcification rates being significant at only four locations. Rates of sea temperature warming at locations in the Andaman Sea (Indian Ocean) (ca. 1.3 °C per decade) were almost twice those in the South China Sea (Pacific Ocean) (ca. 0.7 °C per decade), but this was not reflected in the magnitude of calcification declines at corresponding locations. Considering that massive Porites spp. are major reef builders around Southeast Asia, this region-wide growth decline is a cause for concern for future reef accretion rates and resilience. However, this study suggests that the future rates and patterns of change within the region are unlikely to be uniform or dependent solely on the rates of change in the thermal environment.

Coral mucus: the properties of its constituent mucins.

The gel-forming properties of mucus are closely related to its functioning; although there is limited information available relating to coral mucus gels. The present study investigates coral mucus glycoprotein using rheological methods. We demonstrate the presence of a high-molecular-weight polymeric glycoprotein similar to that found in vertebrates, capable of forming a gel. The milked mucus exuded mostly from the oral cavity of corals is not a gel; however, it does show a tendency to form a gel upon concentration. Such results indicate the potential for corals to produce two different kinds of mucus, each potentially capable of performing different functions.

Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers.

Human epidermis elaborates two small cationic, highly hydrophobic antimicrobial peptides (AMP), beta-defensin 2 (hBD2), and the carboxypeptide cleavage product of human cathelicidin (hCAP18), LL-37, which are co-packaged along with lipids within epidermal lamellar bodies (LBs) before their secretion. Because of their colocalization, we hypothesized that AMP and barrier lipid production could be coregulated by altered permeability barrier requirements. mRNA and immunostainable protein levels for mBD3 and cathelin-related antimicrobial peptide (CRAMP) (murine homologues of hBD2 and LL-37, respectively) increase 1-8 hours after acute permeability barrier disruption and normalize by 24 hours, kinetics that mirror the lipid metabolic response to permeability barrier disruption. Artificial permeability barrier restoration, which inhibits the lipid-synthetic response leading to barrier recovery, blocks the increase in AMP mRNA/protein expression, further evidence that AMP expression is linked to permeability barrier function. Conversely, LB-derived AMPs are also important for permeability barrier homeostasis. Despite an apparent increase in mBD3 protein, CRAMP-/- mice delayed permeability barrier recovery, attributable to defective LB contents and abnormalities in the structure of the lamellar membranes that regulate permeability barrier function. These studies demonstrate that (1) the permeability and antimicrobial barriers are coordinately regulated by permeability barrier requirements and (2) CRAMP is required for permeability barrier homeostasis.

Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization.

Ubiquitously expressed focal adhesion kinase (FAK), linked to multiple intracellular signaling pathways, has previously been shown to control cell motility, invasion, proliferation, and survival. Using mice with a keratinocyte-restricted deletion of fak (FAK(K5 KO)), we report here a novel role for FAK: maintenance of adult epidermal permeability barrier homeostasis. Abundant lacunae of unprocessed lipids in stratum corneum (SC) of FAK(K5 KO) mice and delayed barrier recovery pointed to malfunction of pH-dependent enzymes active in extracellular space of SC. Measuring the SC pH gradient showed significantly more neutral pH values in FAK(K5 KO) mice, suggesting the importance of FAK for acidification. Moreover, normal functions were restored when FAK(K5 KO) mice were exposed to a surface pH typical of mouse SC (pH = 5.5). Baseline levels and response to barrier disruption of secretory phospholipase A2 isoforms, enzymes that mediate generation of free fatty acids in epidermis, appeared similar in both FAK(K5 KO) and control littermates. We found that the critical SC acidification regulator Na(+)/H(+) exchanger 1 failed to localize to the plasma membrane in FAK-deficient keratinocytes both in vivo and in vitro. Thus, for plasma membrane localization in terminally differentiated keratinocytes, Na(+)/H(+) exchanger 1 requires an intact actin cytoskeleton, which is impaired in FAK-deficient cells.

Glucocorticoid blockade reverses psychological stress-induced abnormalities in epidermal structure and function.

Many cutaneous disorders are adversely affected by psychological stress (PS), but the responsible mechanisms are poorly understood. Recent studies have demonstrated that PS decreases epidermal proliferation and differentiation, impairs permeability barrier homeostasis, and decreases stratum corneum integrity. PS also increases the production of endogenous glucocorticoids (GC), and both systemic and topical GC cause adverse effects on epidermal structure and function similar to those observed with PS. We therefore hypothesized that increased endogenous GC in PS mediates its adverse cutaneous effects. To test this hypothesis, we used two independent approaches, administering either RU-486, a GC receptor antagonist that inhibits GC action, or antalarmin, a corticotropin-releasing hormone (CRH) receptor antagonist that prevents increased GC production in the face of PS. Inhibition of either GC action or production prevents the PS-induced decline in epidermal cell proliferation and differentiation, impairment in permeability barrier homeostasis, and decrease in stratum corneum (SC) integrity. Moreover, the pathophysiological basis for the abnormality in permeability barrier homeostasis; i.e., decreased lamellar body production and secretion, is restored toward normal by inhibition of GC action. Similarly, the mechanistic basis for the decrease in SC integrity, i.e., a reduction in corneodesmosomes, is also normalized by inhibition of GC action. Thus many of the adverse effects of PS on epidermal structure and function can be attributed to increased endogenous GC and conversely, approaches that either reduce GC production or action might benefit cutaneous disorders that are provoked or exacerbated by PS.

Serine protease signaling of epidermal permeability barrier homeostasis.

Evidence is growing that protease-activated receptor-2 (PAR-2) plays a key role in epithelial inflammation. We hypothesized here that PAR-2 plays a central role in epidermal permeability barrier homeostasis by mediating signaling from serine proteases (SP) in the stratum corneum (SC). Since the SC contains tryptic- and chymotryptic-like activity, we assessed the influence of SP activation/inhibition on barrier function. Acute barrier disruption increases SP activity and blockade by topical SP inhibitors (SPI) accelerates barrier recovery after acute abrogation. This improvement in barrier function is due to accelerated lamellar body (LB) secretion. Since tryptic SP signal certain downstream responses through PAR-2, we assessed its potential role in mediating the negative effects of SP on permeability barrier. Firstly, PAR-2 is expressed in the outer nucleated layers of the epidermis and most specifically under basal condition to the lipid raft (LR) domains. Secondly, tape stripping-induced barrier abrogation provokes PAR-2 activation, as shown by receptor internalization (i.e. receptor movement from LR to cytolpasmic domains). Thirdly, topical applications of PAR-2 agonist peptide, SLIGRL, delay permeability barrier recovery and inhibit LB secretion, while, conversely, PAR-2 knockout mice display accelerated barrier recovery kinetics and enhanced LB secretion, paralleled by increased LR formation and caveolin-1 expression. These results demonstrate first, the importance of SP/SPI balance for normal permeability barrier homeostasis, and second, they identify PAR-2 as a novel signaling mechanism of permeability barrier, that is, of response linked to LB secretion.

Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-gamma, normalizes epidermal homeostasis in a murine hyperproliferative disease model.

In a murine model of epidermal hyperplasia reproducing some of the abnormalities of several common skin disorders, we previously demonstrated the antiproliferative and pro-differentiating effects of peroxisome proliferator-activated receptor (PPAR)alpha, PPARbeta/delta, and liver X receptor activators. Unlike other subgroups of PPAR activators, thiazolidinediones (TZDs), a family of PPARgamma ligands, did not inhibit keratinocyte proliferation in normal murine skin. Here, we studied the effects of two TZDs, namely ciglitazone (10 mM) and troglitazone (1 mM), in the same murine model where epidermal hyperproliferation was reproduced by repeated barrier abrogation with tape stripping. Topical treatment with ciglitazone and troglitazone resulted in a marked and significant decrease in epidermal thickness. Furthermore, in all TZD-treated groups, we observed a significant decrease in keratinocyte proliferation using proliferating cell nuclear antigen, 5-bromo-2'-deoxyuridine, and tritiated thymidine incorporation. However, using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found no difference in apoptosis between different treatments, emphasizing that it is the antiproliferative role of these activators that accounts for the decrease of epidermal thickness. Finally, using immunohistochemical methods, we determined the effects of ciglitazone on keratinocyte differentiation in this hyperproliferative model. We observed an increased expression of involucrin and filaggrin following ciglitazone treatment, suggesting a pro-differentiating action of TZDs in this model. In summary, topical TZDs significantly reduce epidermal keratinocyte proliferation while promoting differentiation in a murine model of hyperproliferative epidermis. Together, these results suggest that in addition to their metabolic effects currently in use in the treatment of type 2 diabetes, topical TZDs could be considered as potential alternative therapeutic agents in hyperproliferative skin diseases such as psoriasis.

Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity.

We showed recently that short-term increases in stratum corneum (SC) pH are accompanied by minor alterations in permeability barrier homeostasis and SC integrity/cohesion. Since prolonged SC neutralization more closely mirrors clinical situations (i.e., neonatal skin, occupational dermatitis conditions), we assessed here whether sustained elevations of SC pH by long-term application of 1,1,3,3-tetramethylguanidine superbase provoke profound alterations in SC function. Sustained SC neutralization altered not only barrier recovery kinetics but also basal permeability barrier function. These abnormalities were attributable to a decrease in beta-glucocerebrosidase (beta-GlcCer'ase) and acidic sphingomyelinase (aSMase) catalytic activity and enzyme degradation consequent to a pH-induced sustained serine protease (SP) activity. The role of SP in this process was shown by the normalization of enzyme activities/content by co-applied SP inhibitors (SPI). To address whether lipid-processing enzymes are potential substrates for the stratum corneum chymotryptic enzyme (SCCE), protein extracts from human SC were treated for 2 h at 37 degrees C with recombinant active SCCE at pH 7.2. Recombinant SCCE induced a significant decrease in the immunoblotting of both beta-GlcCer'ase or aSMase compared with control experiments performed in the absence of the active SCCE. Finally, with sustained SC neutralization, SC integrity/cohesion deteriorated, attributable to SP-mediated degradation of corneodesmosomes (CD) as well as CD constituent proteins, desmoglein 1. These abnormalities were again reversed by co-applied SPI. In conclusion, prolonged SC neutralization provokes profound abnormalities in SC function, due to pH-induced high SP activity that, in turn, degrades lipid processing enzymes and CD proteins.

Is endogenous glycerol a determinant of stratum corneum hydration in humans?

Although stratum corneum (SC) hydration has been primarily of concern to the cosmetic industry, it serves an important biosensor function. In murine models, not only deiminated products of filaggrin-derived amino acids ("NMF") but also endogenous glycerol from circulation into the epidermis via aquaporin 3 channel and from triglyceride turnover in sebaceous glands (SG) are important determinants. We assessed here whether endogenous glycerol could also be linked to SC hydration in humans. SG-enriched sites are more hydrated than SG-impoverished sites, and SC hydration correlates with both sebum production and SC glycerol content, but the correlation is more significant for SC glycerol content than for sebum content. Moreover, gender-related differences in sebum content are not associated with altered SC hydration. SC hydration is also linked to SC glycerol content in SG-impoverished sites, suggesting a role for non-SG-derived (? from circulation) glycerol in SC hydration. Finally, short-term water immersion produces a parallel decline in SC hydration and SC glycerol content, with glycerol levels returning to normal over several hours. These results suggest that endogenous glycerol of both circulatory and SG origin comprises an H2O-extractable pool that influences SC hydration in humans. These results also provide a rationale for the development of glycerol-containing therapeutic moisturizers.

Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity.

Although many skin disorders, including psoriasis and atopic dermatitis, are adversely affected by psychologic stress (PS), the pathophysiologic link between PS and disease expression remains unclear. Recent studies demonstrated PS-induced alterations in permeability barrier homeostasis, mediated by increased endogenous glucocorticoids. Here, we assessed the mechanisms by which PS alters stratum corneum (SC) function. Insomniac psychologic stress (IPS) altered both barrier homeostasis and SC integrity. IPS decreased epidermal cell proliferation, impaired epidermal differentiation, and decreased the density and size of corneodesmosomes (CD), which was linked to degradation of CD proteins (e.g., desmoglein1). Barrier compromise was linked to decreased production and secretion of lamellar bodies (LB), which in turn could be attributed to a decrease in de novo synthesis of epidermal lipids. Topical physiologic lipids (equimolar cholesterol, ceramides, and free fatty acids) normalized both barrier homeostasis and SC integrity in IPS mice, further evidence that lipid deficiency accounted for these functional abnormalities. Thus, PS inhibition of epidermal lipid synthesis results in decreased LB formation and secretion, as well as decreased CD, compromising both permeability barrier homeostasis and SC integrity. These studies suggest that topical treatment with epidermal physiologic lipids could be beneficial in stress-induced, barrier-associated dermatoses, such as psoriasis and atopic dermatitis.

Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation.

Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-alpha or PPAR-delta activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-gamma activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-gamma activation stimulates keratinocyte differentiation. Additionally, PPAR-gamma activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-gamma activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-gamma activators are mediated by PPAR-gamma, we next examined animals deficient in PPAR-gamma. Mice with a deficiency of PPAR-gamma specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-gamma-deficient epidermis. Although PPAR-gamma activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-gamma-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-gamma activators is mediated by PPAR-gamma. In contrast, PPAR-gamma activators inhibited inflammation in both PPAR-gamma-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-gamma activators does not require PPAR-gamma in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-gamma activators maybe useful in the treatment of cutaneous disorders.

Functional consequences of a neutral pH in neonatal rat stratum corneum.

At birth, neonatal stratum corneum (SC) pH is close to neutral but acidifies with maturation, which can be ascribed, in part, to secretory phospholipase A(2) and sodium/hydrogen antiporter 1 (NHE1) activities. Here we assessed the functional consequences of a neutral SC pH in a newborn rat model. While basal transepidermal water loss rates are near normal, barrier recovery (BR) rates after acute barrier disruption were delayed in newborn animals. The abnormality in barrier homeostasis could be improved by topical applications of an acidic buffer, indicating that barrier abnormality is primarily due to high SC pH. The delay in BR correlated with incompletely processed lamellar membranes and decreased activity of beta-glucocerebrosidase. Inhibition of NHE1 delayed BR after acute barrier perturbation. SC integrity was abnormal in newborn animals. Electron microscopy demonstrated decreased corneodesmosomes (CD) in newborn animals with decreased expression of desmoglein 1 and corneodesmosin. Serine protease activation appears to be responsible for CD degradation in newborn animals, because serine protease activity is increased in the SC and it can be reduced by acidification of the SC. The delay in acidification of neonatal SC results in abnormalities in permeability barrier homeostasis and SC integrity and are likely due to pH-induced modulations in enzyme activity.

Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.

Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.