In this article:
- Dimpling and weak skin
- Biopsies reveal “giant” fat cells
- And “disordered collagen”
- And fibrotic septa
- A comprehensive theory
- Even skinny girls have bloated fat cells
- Hormone changes make it worse
- Men have less subcutaneous fat and less gluteofemoral fat
- Most cellulite creams block fat cell regeneration
- The cellulite boomerang
- Adipeau reverses the cycle
- Validated by the Karolinska Institute
- Results
Cellulite. Explained.
Solving cellulite requires a new take. Fortunately, several elements point to a root cause: First, almost 85% of women have cellulite. This means young women have it and skinny women have it. This is a big clue. Second, men can get cellulite too. But mostly on their bellies. Third, In women, cellulite predominates on thighs and butts. These are three important clues. Source: Khan MH, Victor F, Rao B, Sadick NS. Treatment of cellulite: Part I. Pathophysiology. J Am Acad Dermatol. 2010 Mar;62(3):361-70; PMID: 20159304.
Dimpling and weak skin.
The appearance of cellulite also points to its origins. The two cardinal features of cellulite are: “pits,” deep indentations which, when aligned, form bands. And “nodules,” loose weak skin that gathers between and is pressed up by the pits. Until recently, treatments were targeted separately at the fat, the loose skin or the fibrotic septa. For a review of the treatment strategies, please see: Bass LS, Kaminer MS. Insights Into the Pathophysiology of Cellulite: A Review. Dermatol Surg. 2020 Oct;46 PMID: 32976174; PMCID: PMC7515470.
Biopsies reveal “giant” fat cells.
Compromised vasculature leads to hypoxic conditions and “giant adipocytes” (authors’ term), identified by black arrows.
The adipocytes found in the biopsies of cellulite subjects were termed “giant” by Scarano et al. The hypertrophy is caused by insufficient regeneration. New fat cell formation is limited by insufficient nutrient supply due to poorly vascularized tissue. The lack of oxygenation also stimulates inflammation which further suppressed new fat cell formation. Scarano A, Petrini M, Sbarbati A, Amore R, Iorio EL, Marchetti M, Amuso D. Pilot study of histology aspect of cellulite in seventy patients who differ in BMI and cellulite grading. J Cosmet Dermatol. 2021 Dec;20(12):4024-4031. doi: 10.1111/jocd.14584. Epub 2021 Nov 6. PMID: 34741577.
And “disordered collagen.”
The collagen and elastin structure in cellulite skin is disorganized and fragmented (black arrows identify fragments).
The biopsies of cellulite subjects reveal a dermis structure that is different from normal skin. The collagen and elastin is fragmented and disordered. See Scarano et al in previous slide. Hypertrophic fat cells weaken the skin by secreting inflammatory cytokines that suppress collagen and elastin production by resident fibroblasts. Hypertrophic fat cells also dramatically increase production of matrix metalloproteinase enzymes which degrade collagen and elastin. See Ezure T, Amano S. Negative regulation of dermal fibroblasts by enlarged adipocytes through release of free fatty acids. J Invest Dermatol. 2011 Oct;131(10):2004-9. PMID: 21697886.
And fibrotic septa.
Black arrows point to defective red blood cells. Red arrows point to fibrotic septa.
A comprehensive theory.
Our comprehensive theory connects what we see in the biopsies below the skin – “giant” fat cells living in hypoxic conditions, disordered collagen and elastin in the dermis, creating the weak skin, which is then trapped in nodules by the stiff fibrotic septa. As we shall see this theory also explains phenomenon such as skinny girls getting cellulite, male belly cellulite and the predominance of cellulite in women on thighs and buttocks.
Even skinny girls have bloated fat cells.
Fat tissue in the gluteo-femoral region is less metabolically active than abdominal fat tissue. It is also less well oxygenated than abdominal fat tissue, which can lead to localized areas of hypoxia as we saw in the cellulite biopsies. As discussed above the hypoxia and low grade inflammation leads to less fat cell turnover. This explains how in otherwise skinny subjects, the thighs and buttocks can develop cellulite. The differences in oxygenation of fat tissue are discussed by Vogel et al. Vogel MAA, Jocken JWE, Sell H, Hoebers N, Essers Y, Rouschop KMA, Cajlakovic M, Blaak EE, Goossens GH. Differences in Upper and Lower Body Adipose Tissue Oxygen Tension Contribute to the Adipose Tissue Phenotype in Humans. J Clin Endocrinol Metab. 2018 Oct 1; PMID: 30020463. The differences in metabolic activity are discussed by Christiansen et al, Christiansen MR, Ureña MG, Borisevich D, Grarup N, Martínez JA, Oppert JM, Sørensen TI, Hansen T, Blaak EE, Kilpeläinen TO. Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia. Am J Clin Nutr. 2021 Oct 4;114. PMID: 34254976.
Hormone changes make it worse.
* Significant difference, p<0.05.
Hormones play important roles in determining fat cell regeneration. During puberty, pregnancy and menopause, the collective changes in hormones favor fat storage and lead to increases in fat cell size. For a discussion of body composition and fat cell size changes during menopause, please see Greendale et al. Greendale GA, Sternfeld B, Huang M, Han W, Karvonen-Gutierrez C, Ruppert K, Cauley JA, Finkelstein JS, Jiang SF, Karlamangla AS. Changes in body composition and weight during the menopause transition. JCI Insight. 2019 Mar 7; PMID: 30843880. For a discussion of fat tissue changes during pregnancy, please see Rojas-Rodriguez R, Lifshitz LM, Bellve KD, Min SY, Pires J, Leung K, Boeras C, Sert A, Draper JT, Corvera S, Moore Simas TA. Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus. Diabetologia. 2015 Sep;58(9), PMID: 26067361.
Men have less subcutaneous fat and less gluteofemoral fat.
https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/multimedia/apple-and-pear-body-shapes/img-20006114
Men have less fat mass than women and store the fat more in the abdomen. As discussed above, abdominal fat tissue is more metabolically active than gluteofemoral fat tissue, which makes it less likely that adipocyte hypertrophy will develop, and consequently less likey that cellulite will develop. Tchoukalova YD, Koutsari C, Karpyak MV, Votruba SB, Wendland E, Jensen MD. Subcutaneous adipocyte size and body fat distribution. Am J Clin Nutr. 2008 Jan;87(1):56-63. doi: 10.1093/ajcn/87.1.56. PMID: 18175737.
Most cellulite creams block fat cell regeneration.
The most popular cellulite creams have at least one ingredient that blocks fat cell regeneration or adipogenesis. The most common adipogenesis-blocking ingredient is caffeine, which is present at high levels in guarana extract. L-carnitine is also effective at blocking new fat cell formation. Since these ingredients also reduce fat cell size, initially there may be an improvement in cellulite appearance. However, as regeneration is actively suppressed, ultimately, the fat cells need to increase in size in order to compensate for lower numbers. This sets off a vicious cycle as discussed in the next slide. Please see Lee MS, Lee HJ, Lee HS, Kim Y. L-carnitine stimulates lipolysis via induction of the lipolytic gene expression and suppression of the adipogenic gene expression in 3T3-L1 adipocytes. J Med Food. 2006 Winter;9(4):468-73. PMID: 17201631 and Kim AR, Yoon BK, Park H, Seok JW, Choi H, Yu JH, Choi Y, Song SJ, Kim A, Kim JW. Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes. BMB Rep. 2016 Feb;49(2):111-5. PMID: 26350746.
The cellulite boomerang.
As regeneration declines, fat cell size increases to compensate. Larger fat cells suppress new fat cell formation, creating a vicious cycle. Please see Isakson et al for a discussion of how hypertrophy leads to impaired fat cell regeneration. Isakson P, Hammarstedt A, Gustafson B, Smith U. Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes. 2009 Jul;58(7):1550-7. PMID: 19351711.
Adipeau reverses the cycle.
Validated by the Karolinska Institute.
Our active ingredients can double the number of cells while maintaining or decreasing cell size.
Results.
Results.
Results.
Results.
