Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

Abstract

Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein-protein interactions, and protein stability/ degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

“…Under fasting conditions, lipolysis is promoted to supply sufficient fatty acids to other organs for oxidative metabolism (reviewed in Nielsen et al [6]). On the other hand, excess fat accumulation could accelerate mitochondrial dysfunction, with subsequent insulin resistance in white fat [7,8].…”

Effect of oleic acid supplementation on prostaglandin production in maternal endometrial and fetal allantochorion cells isolated from late gestation ewes

“…Obesity increases the risk of many pregnancy related complications including pre-eclampsia [2], pre-term birth [3], prolonged labour [4] and emergency caesarean section [5]. Obesity is associated with aberrant lipid metabolism and higher circulating concentrations of free fatty acids [6,7]. Women with non-esterified fatty acids (NEFA) levels in the highest tertile were at about twice the risk of spontaneous pre-term birth than those in the lowest tertile [3].…”

“…OA also constituted around 10% of the fatty acids present in amniotic fluid [10] and 30% of total membrane fatty acids in immortalised pregnant human myometrial cells [11]. Circulating NEFA concentrations including OA also rise during negative energy balance when body lipids are mobilised to supply extra energy [7]. In addition, OA is a principal effective ingredient within foodstuffs such as olive oil and peanuts which are believed to have positive effects on human health, such as protection from cardiovascular disease [12,13].…”

Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

“…Adipolysis is the breakdown of accumulated triglyceride stores in differentiated adipocytes during energy deprivation by releasing glycerol and free fatty acids. This process is achieved by sequential action of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase (MGLL) through the production of cAMP (cyclic Adenosine Monophosphate) which subsequently activates PKA (Protein Kinase A) which is considered the main stimulator of lipolysis (Nielsen et al, 2014). According to Harmon and Harp (2001), flavonoids possess the ability to induce lipolysis in 3T3-L1 adipocytes.…”