The Role of Fat Reducing Agents on Adipocyte Death and Adipose Tissue Inflammation

Abstract

Deoxycholic Acid (DCA), which is an FDA-approved compound for the reduction of submental fat, has evolved through an unanticipated and surprising sequence of events. Initially, it was used as a solvent for Phosphatidylcholine (PDC), which was thought to promote lipolysis, but it was later proven to be the bioactive component of the formula and is currently widely used as Kybella. It has also been used off-label to treat other types of fat deposits like lipomas, HIV lipodystrophy, and excess orbital fat. Despite widespread clinical use, there has been no consensus clarifying the mechanisms of DCA and PDC alone or in combination. Furthermore, despite PDC’s removal from the FDA-approved formula, some studies do suggest it plays an important role in fat reduction. To provide some clarity, we conducted a PubMed search and reviewed 41 articles using a comprehensive list of terms in three main categories, using the AND operator: 1) Phosphatidylcholines 2) Deoxycholic Acid, and 3) Lipoma. We isolated articles that studied PDC, DCA, and a PDC/DCA compound using cell biology, molecular and genetic techniques. We divided relevant articles into those that studied these components using histologic techniques and those that utilized specific cell death and lipolysis measurement techniques. Most morphologic studies indicated that PDC/DCA, DCA, and PDC, all induce some type of cell death with accompanying inflammation and fibrosis. Most morphologic studies also suggest that PDC/DCA and DCA alone are non-selective for adipocytes. Biochemical studies describing PDC and DCA alone indicate that DCA acts as a detergent and rapidly induces necrosis while PDC induces TNF-α release, apoptosis, and subsequent enzymatic lipolysis after at least 24 hours. Additional papers have suggested a synergistic effect between the two compounds. Our review integrates the findings of this growing body of literature into a proposed mechanism of fat reduction and provides direction for further studies.

Success Rate of Buccal Fat Pad Removal in Cases of Previous Injection Lipolysis of the Cheeks: A Comparative Analysis

“…It is important to note that the existing literature suggests that injection lipolysis triggers a specific inflammatory response in adipose tissue, leading to cellular death, necrosis of fat tissue, and subsequent tissue fibrosis. [19][20][21] Further, the presence of fibrosis resulting from prior cheek injection lipolysis complicates the removal of the buccal fat pad, posing significant risks to the integrity of the buccal branch of the facial nerve and parotid duct. Buccal fat pad removal is particularly advantageous for individuals with round and chubby faces, as a substantial volume of fat should be excised to achieve an aesthetically pleasing result.…”

Chenodeoxycholic Acid-Loaded Nanoparticles Are Sufficient to Decrease Adipocyte Size by Inducing Mitochondrial Function

“…Bile acids (BAs) have been used as therapeutics for a variety of diseases, including primary biliary cirrhosis, cholesterol gallstone dissolution (Ursodiol; Chenodiol), , BA synthesis disorder (Cholbam), and local fat reduction (Kybella) . The FDA-approved NaDCA (Kybella) is used to treat double chin (submental fat depot), but the multiple injection regimen needed for this treatment causes bruising, pain, swelling, and vascular injury as side effects. − In this report, we developed CDCA-loaded gelatin nanoparticles (CDCA-GNPs) with a controlled release profile and demonstrated that like NaDCA, CDCA-GNPs reduced subcutaneous adipocyte size.…”

“…For instance, subcutaneous injection of sodium deoxycholic acid (NaDCA), Kybella, has been approved by the Food and Drug Administration (FDA) as a nonsurgical approach for reducing double chin. 8 However, the high doses and multiple injections of NaDCA needed to achieve these effects, which function primarily by promoting adipocyte cell death and subsequent inflammation within adipose tissue, restrict its application. 8 Unlike cytolysis, the utilization of lipids by promoting mitochondrial function is a well-documented alternative approach for reducing fat.…”

“…8 However, the high doses and multiple injections of NaDCA needed to achieve these effects, which function primarily by promoting adipocyte cell death and subsequent inflammation within adipose tissue, restrict its application. 8 Unlike cytolysis, the utilization of lipids by promoting mitochondrial function is a well-documented alternative approach for reducing fat. 9−11 In addition to being detergents, BAs also act as signaling molecules by activating membrane G protein-coupled receptor Takeda G protein-coupled receptor 5 (TGR5) and nuclear receptor farnesoid X receptor (FXR), to regulate lipid metabolism.…”

“…Bile acids (BAs), the body’s natural detergents known to solubilize fat in the intestine, can also promote fat burning and protect against metabolic dysfunction. − Thus, these molecules can be repurposed as fat-reducing agents. For instance, subcutaneous injection of sodium deoxycholic acid (NaDCA), Kybella, has been approved by the Food and Drug Administration (FDA) as a nonsurgical approach for reducing double chin . However, the high doses and multiple injections of NaDCA needed to achieve these effects, which function primarily by promoting adipocyte cell death and subsequent inflammation within adipose tissue, restrict its application …”