Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues

Abstract

De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. Dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases. Thus, the lipogenic pathway may provide a new therapeutic opportunity for combating various pathological conditions that are associated with dysregulated lipid metabolism. Hepatic DNL has been well documented, but lipogenesis in adipocytes and its contribution to energy homeostasis and insulin sensitivity are less studied. Recent reports have gained significant insights into the signaling pathways that regulate lipogenic transcription factors and the role of DNL in adipose tissues. In this review, we will update the current knowledge of DNL in white and brown adipose tissues with the focus on transcriptional, post-translational, and central regulation of DNL. We will also summarize the recent findings of adipocyte DNL as a source of some signaling molecules that critically regulate energy metabolism.

Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells

“…Adipocyte differentiation can activate key lipogenic enzymes such as fatty acid synthase (FAS) and acetyl CoA carboxylase (ACC). FAS promotes the synthesis and storage of triglyceride in adipocytes and ACC converts malonyl-CoA into palmitate [7]. We examined the effects of D and DA on expression levels of lipogenic markers 12 days after adipogenic induction with ADM treatment.…”

“…Adipocyte differentiation from ASCs is regulated by key adipogenic transcription factors, including members of the CCAAT/enhancer binding protein (C/EBP) family and peroxisome proliferator-activated receptor γ (PPAR-γ) [5,6]. These transcription factors are crucial for expression of adipocyte-specific genes, such as adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) [7]. Moreover, increasing evidences suggest that β-catenin inhibit adipogenesis by blocking interaction between the TCF/LEF-binding domain of β-catenin and the catenin-binding domain of C/EBPα/and PPARγ.…”

Prevenção da obesidade e da resistência à insulina através do treinamento físico aeróbio: papel do sistema renina angiotensina no tecido adiposo branco

“…Assim, é possível que o TFA reduza a sinalização da insulina no TAB-PE, contribuindo para diminuir a lipogênese de novo nos grupos treinados (SMITH & KAHN, 2016;SONG et al, 2018). Por outro lado, o resultado no grupo SED-CAF pode ser um indicativo de RI periférica que coincide com os prejuízos apresentados por esse grupo no TTG e no TTI.…”

“…Finalmente, as enzimas glicerol-3 fosfato aciltransferase (GPAT) e diacilglicerol aciltransferase (DGAT) são responsáveis pela parte final do processo esterificando a acil-CoA juntamente com glicerol-3-fosfato em TG (BÓDIS & RODEN, 2018;SHI & CHENG, 2008;TAKEUCHI et al, 2009). Já a lipogênese de novo, consiste em processos metabólicos a partir de substratos diferentes de lipídeos que resultam na biossíntese e incorporação de TG nas gotículas de gordura do adipócito (BÓDIS & RODEN, 2018;SONG et al, 2018;FONSECA-ALANIZ et al, 2006). Esse processo ocorre pela conversão da citrato em acetil-CoA pela enzima ATP citrato liase (ACL) (WAKIL et al,1983).…”

“…Esse processo ocorre pela conversão da citrato em acetil-CoA pela enzima ATP citrato liase (ACL) (WAKIL et al,1983). A Acetil-CoA formada é convertida a malonil-CoA pela enzima ácido graxo carboxilase (ACC) que será utilizada como substrato para síntese de TG pela enzima ácido graxo sintase (FAS) (BÓDIS & RODEN, 2018;SMITH & KAHN, 2018;SONG et al, 2018;FONSECA-ALANIZ et al, 2006). YOON et al, 2006), aumento da captação de glicose nos adipócitos (WU et al, 2003), aumento da secreção de insulina e redução da concentração plasmática de glicose (YAMAGUCHI et al, 2002).…”