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Linking diet to acne metabolomics, inflammation, and comedogenesis: an update.

Melnik BC - Clin Cosmet Investig Dermatol (2015)

Bottom Line: Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate.Free palmitate functions as a "danger signal," stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation.Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Germany.

ABSTRACT
Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1) hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs). Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a "danger signal," stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation, and comedogenesis via interleukin-1α release. Thus, diet-induced metabolomic alterations promote the visible sebofollicular inflammasomopathy acne vulgaris. Nutrition therapy of acne has to increase FoxO1 and to attenuate mTORC1/SREBP-1c signaling. Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats. A paleolithic-like diet enriched in vegetables and fish is recommended. Plant-derived mTORC1 inhibitors and ω-3-PUFAs are promising dietary supplements supporting nutrition therapy of acne vulgaris.

No MeSH data available.


Related in: MedlinePlus

Acne vulgaris: a Western diet-induced sebofollicular inflammasomopathy.Abbreviations: IGF-1, insulin-like growth factor 1; BCAAs, branched-chain amino acids; miR21, microRNA-21; FoxO1, forkhead box class O1; mTORC1, mechanistic target of rapamycin complex 1; AR, androgen receptor; PPARγ, peroxisome proliferator-activated receptor-γ; LXRα, liver X receptor-α; SREBP1c, sterol response element binding protein 1c; Δ6D, Δ6-desaturase; SCD, stearoyl-CoA desaturase; TG, triglyceride; P. acnes, Propionibacterium acnes; QS, quorum sensing; C16:0, palmitic acid; C18:1, oleic acid; TLR2, toll-like receptor 2; NLRP3, Nod-like receptor family, pyrin domain containing 3 inflammasome; IL-1β, interleukin-1β; Th17, Th17 T-cell; IL-17, interleukin-17, IL-1α, interleukin-1α.
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f1-ccid-8-371: Acne vulgaris: a Western diet-induced sebofollicular inflammasomopathy.Abbreviations: IGF-1, insulin-like growth factor 1; BCAAs, branched-chain amino acids; miR21, microRNA-21; FoxO1, forkhead box class O1; mTORC1, mechanistic target of rapamycin complex 1; AR, androgen receptor; PPARγ, peroxisome proliferator-activated receptor-γ; LXRα, liver X receptor-α; SREBP1c, sterol response element binding protein 1c; Δ6D, Δ6-desaturase; SCD, stearoyl-CoA desaturase; TG, triglyceride; P. acnes, Propionibacterium acnes; QS, quorum sensing; C16:0, palmitic acid; C18:1, oleic acid; TLR2, toll-like receptor 2; NLRP3, Nod-like receptor family, pyrin domain containing 3 inflammasome; IL-1β, interleukin-1β; Th17, Th17 T-cell; IL-17, interleukin-17, IL-1α, interleukin-1α.

Mentions: IGF-1 plays a pivotal role in sebaceous lipogenesis.62,63 Downstream of IGF-1/PI3K/AKT signaling respond four key lipogenic transcription factors: the AR,18,19,27,28 peroxisome proliferator-activated receptor-γ (PPARγ),64–67 liver X receptor-α (LXRα),68,69 and sterol response element binding protein-1c (SREBP-1c),62,63,70 which are all negatively regulated by FoxO1 (Figure 1).18,19,27,28,71–77 IGF-1 stimulated SREBP-1 expression and induced lipogenesis in SEB-1 sebocytes via activation of the PI3K/AKT pathway.63 Mirdamadi et al35 confirmed that IGF-1 suppresses nuclear FoxO1 in SZ95 sebocytes associated with increased lipogenesis. Under conditions of nutrient excess and high-insulin/IGF-1 signaling, downregulated nuclear FoxO1 thus derepresses all master transcription factors of sebaceous lipogenesis such as AR, PPARγ, LXRα, and SREBP-1c. In fact, Kwon et al78 observed decreased SREBP-1 expression in facial acne skin after 4 weeks of a low glycemic load diet. Notably, acne-free Kitavan islanders,79 who are still exposed to a paleolithic diet (less-hyperglycemic carbohydrates, no milk and dairy products, but plenty of fish intake), exhibit low basal insulin serum levels that are only half of those of Europeans living under conditions of Western neolithic diet.80 Incubation of epithelial cells with IGF-1-deficient serum of Laron patients exhibited increased nuclear FoxO1 activity and decreased expression of TOR.14 Notably, excessive meat intake is another characteristic feature of Western diet. Recent epidemiological evidence underlines that low protein intake is associated with a major reduction in serum IGF-1 in the middle-aged population.81


Linking diet to acne metabolomics, inflammation, and comedogenesis: an update.

Melnik BC - Clin Cosmet Investig Dermatol (2015)

Acne vulgaris: a Western diet-induced sebofollicular inflammasomopathy.Abbreviations: IGF-1, insulin-like growth factor 1; BCAAs, branched-chain amino acids; miR21, microRNA-21; FoxO1, forkhead box class O1; mTORC1, mechanistic target of rapamycin complex 1; AR, androgen receptor; PPARγ, peroxisome proliferator-activated receptor-γ; LXRα, liver X receptor-α; SREBP1c, sterol response element binding protein 1c; Δ6D, Δ6-desaturase; SCD, stearoyl-CoA desaturase; TG, triglyceride; P. acnes, Propionibacterium acnes; QS, quorum sensing; C16:0, palmitic acid; C18:1, oleic acid; TLR2, toll-like receptor 2; NLRP3, Nod-like receptor family, pyrin domain containing 3 inflammasome; IL-1β, interleukin-1β; Th17, Th17 T-cell; IL-17, interleukin-17, IL-1α, interleukin-1α.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507494&req=5

f1-ccid-8-371: Acne vulgaris: a Western diet-induced sebofollicular inflammasomopathy.Abbreviations: IGF-1, insulin-like growth factor 1; BCAAs, branched-chain amino acids; miR21, microRNA-21; FoxO1, forkhead box class O1; mTORC1, mechanistic target of rapamycin complex 1; AR, androgen receptor; PPARγ, peroxisome proliferator-activated receptor-γ; LXRα, liver X receptor-α; SREBP1c, sterol response element binding protein 1c; Δ6D, Δ6-desaturase; SCD, stearoyl-CoA desaturase; TG, triglyceride; P. acnes, Propionibacterium acnes; QS, quorum sensing; C16:0, palmitic acid; C18:1, oleic acid; TLR2, toll-like receptor 2; NLRP3, Nod-like receptor family, pyrin domain containing 3 inflammasome; IL-1β, interleukin-1β; Th17, Th17 T-cell; IL-17, interleukin-17, IL-1α, interleukin-1α.
Mentions: IGF-1 plays a pivotal role in sebaceous lipogenesis.62,63 Downstream of IGF-1/PI3K/AKT signaling respond four key lipogenic transcription factors: the AR,18,19,27,28 peroxisome proliferator-activated receptor-γ (PPARγ),64–67 liver X receptor-α (LXRα),68,69 and sterol response element binding protein-1c (SREBP-1c),62,63,70 which are all negatively regulated by FoxO1 (Figure 1).18,19,27,28,71–77 IGF-1 stimulated SREBP-1 expression and induced lipogenesis in SEB-1 sebocytes via activation of the PI3K/AKT pathway.63 Mirdamadi et al35 confirmed that IGF-1 suppresses nuclear FoxO1 in SZ95 sebocytes associated with increased lipogenesis. Under conditions of nutrient excess and high-insulin/IGF-1 signaling, downregulated nuclear FoxO1 thus derepresses all master transcription factors of sebaceous lipogenesis such as AR, PPARγ, LXRα, and SREBP-1c. In fact, Kwon et al78 observed decreased SREBP-1 expression in facial acne skin after 4 weeks of a low glycemic load diet. Notably, acne-free Kitavan islanders,79 who are still exposed to a paleolithic diet (less-hyperglycemic carbohydrates, no milk and dairy products, but plenty of fish intake), exhibit low basal insulin serum levels that are only half of those of Europeans living under conditions of Western neolithic diet.80 Incubation of epithelial cells with IGF-1-deficient serum of Laron patients exhibited increased nuclear FoxO1 activity and decreased expression of TOR.14 Notably, excessive meat intake is another characteristic feature of Western diet. Recent epidemiological evidence underlines that low protein intake is associated with a major reduction in serum IGF-1 in the middle-aged population.81

Bottom Line: Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate.Free palmitate functions as a "danger signal," stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation.Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Germany.

ABSTRACT
Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1) hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs). Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a "danger signal," stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation, and comedogenesis via interleukin-1α release. Thus, diet-induced metabolomic alterations promote the visible sebofollicular inflammasomopathy acne vulgaris. Nutrition therapy of acne has to increase FoxO1 and to attenuate mTORC1/SREBP-1c signaling. Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats. A paleolithic-like diet enriched in vegetables and fish is recommended. Plant-derived mTORC1 inhibitors and ω-3-PUFAs are promising dietary supplements supporting nutrition therapy of acne vulgaris.

No MeSH data available.


Related in: MedlinePlus