There is an elaborate network of adipogenic transcription factors which include transcriptional activators, co-activators and repressors that coordinate the expression of essential proteins involved in the formation of mature fat cells through several important signaling pathways. On one hand these factors initiate and regulate the transcriptional cascade during development of new fat cells. These same factors also regulate the expression of essential metabolic enzymes, signaling components, and adipokines in the mature fat cell. By controlling these events, these factors maintain the differentiated state by allowing fat cells to perform their functions. The human KLF family has 17 members, which are expressed in a variety of cell types[
18‐
20]. Several members of mammalian KLFs including KLF2-KLF7, KLF11, KLF14, and KLF15 have important roles in fat metabolism[
13‐
17]. For instance, KLF2 is widely expressed in adipose tissue while functioning as a negative regulator of adipogenesis. Forced expression of KLF3 blocks adipocyte differentiation in 3 T3-L1 cell lines through a direct association with
C/ebpα promoter, whereas a decrease in KLF3 prevents differentiation[
17]. Birsoy and colleagues[
16] showed that KLF4 is a regulator of early adipogenesis induced in 3 T3-L1 cells within 30 min after exposure to a standard cocktail of insulin, glucocorticoids, and IBMX. Their data further suggests that eliminating KLF4 activity inhibits adipogenesis while down-regulating C/EBPβ. Most recently, Lee and Colleagues[
21] observed that mammalian KLF4 mediates metabolic functions including food intake and energy balance through regulation of human ghrelin expression via binding to a KLF-responsive region in the promoter. Ghrelin is an orexigenic hormone that is secreted from the stomach during fasting, which stimulates the release of growth hormone from the pituitary gland and regulates both food intake and energy balance[
22,
23]. While KLF15 promotes adipogenesis by its expression in adipocytes and myocytes[
24], it also up-regulates GLUT4 in both adipose and muscle tissues[
25,
26]. Human KLF14 controls many essential genes that are linked to a range of metabolic conditions including obesity, cholesterol, insulin and glucose levels. Recently, human KLF14 has been identified as a regulator linking obesity to the T2D; KLF14 acts as a master trans-regulator of adipose gene expression in T2D and HDL-cholesterol associated cis-acting eQTL[
27]. Thus KLF14 acts as a master switch controlling processes that link changes in the behavior of subcutaneous fat to disorder in muscle and liver that contributes to diabetes, obesity and other conditions[
27]. This indicates that small changes in one master regulator gene can cause a cascade of other effects in other genes. KLF plays key role in over all energy homeostasis by its regulation of important factors involved in food intake, fat storage and utilization. For instance, KLF7 acts as negative regulator of adipogenesis. In the insulin secreting cell line (HIT-T15 cells), over expression of KLF7 significantly suppressed glucose-induced secretion of insulin and reduced the expression of adiponectin and other adipogenesis related genes, including leptin, PPARγ and C/EBPα, thereby, blocking adipogenesis[
28,
29]. The hormones, leptin and insulin are known as circulating indicators of adiposity with overlapping physiological and intracellular signaling capabilities. KLF7 plays an important role in the pathogenesis of T2D and it controls both leptin and insulin to maintain energy balance.