Lower intake of dietary protein is associated with improved metabolic health and reduced rates of age-associated diseases in humans, while low protein (LP) diets improve fitness and extend the lifespan of diverse animal species. Paradoxically, many athletes and bodybuilders consume high protein (HP) diets and protein or branched-chain amino acid supplements, yet remain fit and metabolically healthy. Here, we examine the effect of weight pulling, a validated progressive resistance exercise training regimen in mice fed either a LP diet or an isocaloric HP diet. We find that sedentary HP-fed male C57BL/6J mice gain significantly more fat mass than sedentary mice fed a LP diet, despite not consuming more calories. Resistance exercise was protective against this effect, blocking excess fat gain overall and in specific fat depots in HP-fed mice, but did not alter fat mass gain or distribution in LP-fed mice. In accordance with the widespread belief that high protein diets help promote muscle mass gain, the HP diet augmented the hypertrophy of the soleus, flexor digitorum longus (FDL) and the forearm flexor complex that occurred in response to exercise. While strength increased more rapidly in HP-fed mice, the maximum strength pulled by LP and HP-fed mice after 12 weeks was indistinguishable. Our results confirm the widespread belief that HP diets can augment muscle hypertrophy and strength gain induced by resistance exercise without negative metabolic consequences, while demonstrating that LP diets may be relatively advantageous in the sedentary. The results here highlight the need to consider both dietary composition and activity levels, not simply calories, when taking a precision nutrition approach to health.
A rapid increase in the global prevalence of skin inflammatory diseases like psoriasis cannot be attributed to genetics alone. Environmental factors including major ubiquitous organic pollutants like polycyclic aromatic hydrocarbons (PAHs) could contribute to their pathophysiology. Benzo[a]pyrene (BaP) is one of the PAH that is generated mainly from cigarette smoke, wood‐burning, automobile exhaust etc. The molecular mechanisms that lead to inflammatory skin diseases following exposure to BaP are not well elucidated, though there are suggestions that these responses could be mediated by aryl hydrocarbon receptor (AhR), a xenobiotic sensor. To investigate the effect of BaP exposure on skin inflammation in a mouse psoriatic model, the dorsal skin of naïve C57BL/6 mice was shaved (48h prior to exposure) and exposed to 62.5mg of 5% imiquimod (IMQ) cream once daily for five days. For assessing the initiation or exacerbation of psoriasis from exposure to BaP, mice were exposed 64μg BaP in 50μl acetone for five days before IMQ application [BaP+IMQ] or for five days together with the IMQ [(BaP+IMQ)] application. Following the analysis and scoring of clinical lesions, mice were sacrificed, and skin sections were analyzed for inflammation‐related histopathological and molecular changes. BaP exposure together with IMQ exacerbated IMQ‐induced psoriatic inflammatory lesions including the skin bi‐fold thickness, epidermal and dermal thickness, hyperkeratosis, dermal fibrosis, neutrophil infiltration, neutrophil degeneration and mast cell degranulation. Molecular analysis on the skin samples to further elucidate the effect BaP on IMQ‐induced inflammatory markers such as neutrophil infiltration, macrophages, inflammatory cytokines that could exacerbate psoriasis is being carried out. In other studies, defining the role of AhR in BaP‐induced biological, molecular, and metabolic alterations in mouse skin, concomitant treatment with AhR antagonist CH‐223191 was given before BaP+IMQ treatment. The antagonist treatment before the (BaP+IMQ) treatment abrogated the BaP‐caused increase in epidermal and dermal thickness in psoriatic mice. The effect of the AhR inhibitor on other biological and molecular psoriatic parameters that are exacerbated on exposure to BaP are also being analyzed to decipher the role of AhR in BaP‐induced and/or exacerbation in inflammatory skin diseases like psoriasis. Support or Funding Information Skaggs Scholars Program Grant, University of Colorado Denver and Start‐up Fund to Neera Tewari‐Singh, Michigan State University
Emerging evidence suggests that environmental chemicals, mainly the organic pollutants like polycyclic hydrocarbons (PAHs), could contribute to the pathophysiology of several chronic inflammatory skin diseases like atopic dermatitis and psoriasis. Benzo[a]pyrene (BaP), the main source of atmospheric PAH, is generated mainly from cigarette smoke, wood‐burning and automobile exhaust. Several reports suggest that the inflammatory effects exerted by BaP could be mediated via the aryl hydrocarbon receptor (AhR) signaling pathway. AhR ligands exert the antioxidative pathway triggered by injury and inflammation, and could activate the nuclear factor‐erythroid 2‐related factor‐2 (NRF2). Pathology of Psoriasis includes acanthosis, hyperkeratosis, and parakeratosis of the epidermis, invasion of neutrophils into the epidermis as well as an inflammatory response. BaP exposure could exacerbate the inflammatory pathology of psoriasis; however, comprehensive studies to assess this and decipher the molecular mechanisms involved, remain elusive. In the present study, we evaluated the effect of BaP on mouse skin psoriasis. For generating psoriasis, the dorsal skin of C57BL/6 male and female mice was shaved and exposed to 62.5mg of 5% imiquimod (IMQ) cream once daily for five days. To study the effect of BaP in the exacerbation of IMQ‐ induced psoriasis, mice were exposed to 64µg BaP in 50µl acetone for five days before IMQ application [BaP+IMQ] or for five days together with the IMQ [(BaP+IMQ)] application. Histopathological analysis showed that BaP exposure together with IMQ exacerbated IMQ‐induced psoriatic inflammatory lesions including the skin bi‐fold thickness, epidermal and dermal thickness, acanthosis, hyperkeratosis, dermal fibrosis and neutrophil infiltration. Our ongoing molecular studies show that the exposure of BaP in IMQ‐induced psoriatic mice elevated the expression of inflammatory markers like COX‐2, MMP9, myeloperoxidase (maker of neutrophil infiltration) and NRF2. Increased expression of these markers suggests that BaP could activate inflammatory pathways and further elevate the skin inflammation in IMQ induced psoriasis. Further mechanistic studies are underway to evaluate the pathways involved in BaP‐induced exacerbation of psoriasis.
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