De Novo Lipogenesis as a Source of Second Messengers in Adipocytes

Abstract

Purpose of review: Obesity is a major risk factor for Type 2 Diabetes. Although adipose tissue allows storage of excess calories in periods of overnutrition, in obesity, adipose tissue metabolism becomes dysregulated and can promote metabolic diseases. This review discusses recent advances in understandings how adipocyte metabolism impacts metabolic homeostasis. Recent findings: The ability of adipocytes to synthesize lipids from glucose is a marker of metabolic fitness, e.g. low de novo lipogenesis (DNL) in adipocytes correlates with insulin resistance in obesity. Adipocyte DNL may promote synthesis of special "insulin sensitizing" signaling lipids that act hormonally. However, each metabolic intermediate in the DNL pathway (i.e. citrate, acetyl-CoA, malonyl-CoA, and palmitate) also has second messenger functions. Mounting evidence suggests these signaling functions may also be important for maintaining healthy adipocytes. Summary: While adipocyte DNL contributes to lipid storage, lipid precursors may have additional second messenger functions critical for maintaining adipocyte health, and thus systemic metabolic homeostasis.

Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

“…In nutrient-rich conditions, citrate, which is an intermediate of the TCA cycle in mitochondria, is shuttled into the cytosol through the citrate carrier [ 49 ]. Citrate is then converted into oxaloacetate and acetyl-coenzyme A by ATP-citrate lyase [ 50 ]. Subsequently, acetyl-CoA is used for FA synthesis [ 50 ].…”

“…Citrate is then converted into oxaloacetate and acetyl-coenzyme A by ATP-citrate lyase [ 50 ]. Subsequently, acetyl-CoA is used for FA synthesis [ 50 ]. In fact, PGC-1α reportedly induces lipogenesis by the production of citrate in tumors, thereby promoting tumor growth [ 51 ].…”

Transcriptional and epigenetic control of adipocyte remodeling during obesity

“…In the presence of high blood glucose levels, insulin is released from β cells of the pancreas, promoting glucose uptake in adipocytes. Within adipocytes, glucose has different potential destinies (12). It can be metabolized into acetyl coenzyme A (CoA), a substrate for the synthesis of endogenous FFAs through de novo lipogenesis, or, primarily, it is metabolized into glycerol, an important substrate for the esterification of FFAs (12).…”

“…Within adipocytes, glucose has different potential destinies (12). It can be metabolized into acetyl coenzyme A (CoA), a substrate for the synthesis of endogenous FFAs through de novo lipogenesis, or, primarily, it is metabolized into glycerol, an important substrate for the esterification of FFAs (12). The FFAs used for triglyceride production in adipocytes come mainly from circulating triglycerides or lipoprotein hydrolyzed by the key enzyme lipoprotein lipase (LPL) and transported into the adipocytes by scavenger receptor CD36 or fatty acid binding proteins (13).…”

Htd2 deficiency-associated suppression of α-lipoic acid production provokes mitochondrial dysfunction and insulin resistance in adipocytes

“…In the process of obesity, adipose tissues go through dynamic and complex cellular changes to expand tissue size via either hypertrophy (increase in size of existing adipocytes) or hyperplasia (formation of new adipocytes through adipogenesis from preadipocytes) [ 5 , 10 ]. Both activities involve fatty acid synthase (FASN) mediated De Novo lipogenesis pathway, which utilizes citrate from mitochondrial TCA cycle to synthesize palmitate with the help of ATP citrate lyase and acetyl-CoA carboxylase [ 11 ]. It was reported that FASN is closely involved in the regulation of food intake, body weight and obesity via modulating adipocyte functionality [ [12] , [13] , [14] ].…”