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Fat Targeted Proapoptotic Peptide - CKGGRAKDC-GG-D(KLAKLAK)2 - 5mg
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Price: $ 200.00 

Fat Targeted Proapoptotic Peptide - CKGGRAKDC-GG-D(KLAKLAK)2 - 5mg

Item 12761

Reversal of obesity by targeted ablation of adipose tissue

Obesity is an increasingly prevalent human condition in developed societies. Despite major progress in the understanding of the molecular mechanisms leading to obesity, no safe and effective treatment has yet been found. Here, we report an antiobesity therapy based on targeted induction of apoptosis in the vasculature of adipose tissue. We used in vivo phage display to isolate a peptide motif (sequence CKGGRAKDC) that homes to white fat vasculature. We show that the CKGGRAKDC peptide associates with prohibitin, a multifunctional membrane protein, and establish prohibitin as a vascular marker of adipose tissue. Targeting a proapoptotic peptide to prohibitin in the adipose vasculature caused ablation of white fat. Resorption of established white adipose tissue and normalization of metabolism resulted in rapid obesity reversal without detectable adverse effects. Because prohibitin is also expressed in blood vessels of human white fat, this work may lead to the development of targeted drugs for treatment of obese patients.

Kolonin MG,, et al. Nat Med. 2004 Jun;10(6):625-32. Epub 2004 May 09


Figure 3. Physiological effects of treatment with CKGGRAKDC-GG-D(KLAKLAK)2. Cohorts (n = 2 8) of diet-induced obese C57BL/6 mice were subcutaneously injected with 150 g CKGGRAKDC-GG-D(KLAKLAK)2 () or an equimolar mixture of CKGGRAKDC and D(KLAKLAK)2 () peptides daily. (a) Weight loss in response to treatment (average from two independent experiments; see Supplementary Fig. 4 online). (b) The appearance of representative treated and control mice and their epididymal fat depots at the end of the treatment course. (c) Serum concentration of nonessential fatty acids (NEFA; * P < 0.05 versus control), glycerol (** P < 0.05 versus control), triacylglycerol (TAG) and cholesterol at the end of the treatment course. (d) Paraffin sections of livers and soleus skeletal muscle from mice shown in b stained with hematoxylin and eosin showing resorption of fat in livers of mice treated for 4 weeks (scale bar, 50 m). (e) Total lipid content in liver and soleus + gastrocnemius skeletal muscle of treated and control mice at the end of the treatment course. (f) Serum leptin level in treated and control mice after 4 weeks of treatment (* P < 0.0001 versus control). (g) Mean daily food consumption by treated and control mice averaged for the first and second biweekly treatment intervals (weights at 1 and 3 weeks used for calculation), adjusted for body weight. Error bars represent s.d. (a,g) or s.e.m. (c–f).



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