**1. Introduction**

In order to survive and adapt to challenging environment, living organisms have equipped themselves with different mechanisms of energy storage that can be accessed when there is a shortage of food supply. In mammals, fat is mainly stored in adipose tissues [1]. There are two types of adipose tissues: white adipose tissue that stores the majority of the body fat and also functions as an endocrine organ and brown adipose tissue that generates the body heat [2]. In adipocytes, fat is stored in lipid droplets (LDs) in the form of neutral lipids, e.g., triacylglycerol (TAG) and cholesteryl ester (CE). White adipocytes contain unilocular LDs that occupy up to 90% of the cytoplasmic space, while brown adipocytes contain multilocular LDs. Obesity is characterized by both increase in the size and number of white adipocytes [3]. Fat storage in white adipose tissue is essential for proper metabolic homeostasis [4]. In contrast, when fat storage in white adipose tissue is compromised or overwhelmed, the ectopic fat accumulation in non-adipose tissues will result in severe metabolic disorders [5].

Lipodystrophy is an extreme fat storage condition, in which white adipose tissue is selectively lost [6]. Partial or generalized loss of fat in this condition causes an array of complications including insulin resistance, type 2 diabetes and acanthosis nigricans, hypertriglyceridemia, hepatic steatosis, hypertension, polycystic ovarian syndrome, and proteinuric kidney disease [7, 8]. The severity of lipodystrophy depends on the level of adipocyte depletion in the body. Fat loss can occur in nearly

the entire body known as congenital generalized lipodystrophy (CGL) or partial loss in small and discrete areas known as familial partial lipodystrophy (FPLD). While CGL is manifested early in life at birth or soon after, partial fat loss in FPLD occurs during late childhood and puberty. CGL can be determined by measurements of skinfold thickness with calipers or by whole-body magnetic resonance imaging (MRI) scan [9]. Since lipodystrophy is a monogenetic disorder, it can also be diagnosed and confirmed by genotyping.

Lipodystrophy is a very rare genetic disease (1 in 10 million for CGL). Currently, there have been around 300–500 CGL cases and 1000 FPLD cases reported; however, the number of undiagnosed patients is suspected to be three times more [10]. Nearly 20 loci for different subtypes of lipodystrophy have been identified. These genes are implicated in the regulation of either the development of white adipose tissue or the expansion of LDs in white adipocytes. In this chapter, we will outline these lipodystrophy-causative gene loci as well as describe in brief the acquired condition of lipodystrophy.
