ATX-101 for reduction of submental fat

Introduction: Facial esthetics are important for self-esteem. Undesired submental fat (SMF) deposits lead to an unappealing submental profile associated with aging and overweight. Compound ATX-101 is a proprietary formulation of purified synthetic deoxycholic acid for pharmacological submental contouring.

Review areas covered: This reviews covers anatomy of SMF, biochemistry of deoxycholic acid related to adipose tissue and tissue response to injection of ATX-101. Data from clinical trials were analyzed for efficacy and safety.

Methodology: Published studies using PubMed^© database 2000 – 2014 have been analyzed. The terms ‘deoxycholate’, ‘deoxycholic acid’, ‘ATX-101’ and ‘injection lipolysis’ were used.

Results: Deoxycholic acid causes adipocyte breakdown and an inflammatory tissue reaction leading to fat cell reduction and limited fibrosis. Four large clinical Phase III trials demonstrated efficacy of ATX-101 in reduction of SMF measured by validated scales and objective measurements. Patients reported improved psychological features and feeling. Adverse effects were mild and temporary.

Expert opinion: Adipocytolysis of SMF by ATX-101 is an important step forward to the development of approved drugs for reduction of localized fat pads. This could become a growing market.     

Increased Ca 2+-sensitivity of myofibrillar tension in heart failure and its functional implication

In human failing myocardium, an increased Ca ²⁺-sensitivity of myofilament tension development has been described in Triton X skinned cardiac myocytes compared to cardiomyocytes obtained from non-failing human donor hearts. The present study aimed to investigate whether there are functional implications of the increased Ca ²⁺-sensitivity in heart failure and whether alterations of myofilament function are already obvious at earlier stages of heart failure, such as in cardiac hypertrophy or whether alterations of the intracellular Ca ²⁺-homeostasis are able to induce alterations in myofilament function. Ca ²⁺-activated tension development was measured in Triton X-skinned fibers from human failing and non-failing myocardium. Ca ²⁺-sensitivity of myofilament tension development was significantly shifted to the left in human failing myocardium. Plots of diastolic free Ca ²⁺ versus diastolic tension development showed that in a range of similar diastolic Ca ²⁺-concentrations, diastolic tension was significantly enhanced in the failing hearts. The Ca ²⁺/tension relationship was shifted to the right in Triton X-skinned fiber preparations from transgenic renin overexpressing rats (TG(mREN2)27), shown to have concentric hypertrophy. In addition, the Ca ²⁺/tension relationship was unchanged in phospholamban knock-out mice with an increased systolic Ca ²⁺ (and enhanced diastolic Ca ²⁺-load). It is concluded that the increased Ca ²⁺-sensitivity of myofilament tension observed in single cardiomyocytes from failing human myocardium may be a phenomenon also present in multicellular preparations and may contribute to the diastolic dysfunction observed in human heart failure. Alterations of myofilament function occur at very early stages of heart failure and may be species dependent, or dependent on intracellular free Ca ²⁺-levels.