Energy homeostasis is maintained by balancing energy intake and expenditure. Many signals regulating energy intake are conserved between the human and zebrafish. NPY (neuropeptide Y) and AgRP (Agouti-related peptide) are neuropeptide and specifically produced from the AgRP/NPY neuron in arcuate nucleus. Both NPY and AgRP promote the growth of adipose tissue and increased appetite. AgRP/NPY neurons counteract another arcuate nucleus cell population. The POMC (proopiomelanocortin) neurons, which are considered anorexigenic. α-MSH (α-melanocyte-stimulating hormone) is a peptide hormone derived by POMC, to be in part responsible for the decreases in food intake and increases in energy expenditure. α-MSH exerts its effect by binding to the MC4R (melanocortin 4 receptors). We have established obsogenic zebrafish by overexpression orexigenic genes including Agrp, and NPY and four TALEN knock-out obsogenic genes, (Carboxypeptidase E (CPE) , nescient helix loop helix 2 (nhlh2), MC4R and POMC). We also generated zebrafish fat models by transgenic overexpression lipogenic (PPAR-γ, DGAT2, and sar1b) and adipocytic genes (ATF4 and Mdx3). We also generated partially deled POMC gene resulted α-MSH talen knockout mutant. As the insights into our research aims for studying lipid metabolism in those zebrafish models, it is very likely that establishment of compound superobesity fish (SOBF) models for studying the connection between obesity (lipogenesis) and metabolic diseases. To observe lipogenesis gene expression and obesity in SOBFs, we performed feeding tests which SOBFs fed with HFD (high fat diet) and ND(normal diet) and then examined by Nile Red and Oil Red O staining. We demonstrated the application of SOBFs by a high-throughput fluorescence-based assay system. Those results demonstrate that these SOBFs are valuable models for analysis metabolic syndrome and Energy homeostasis.