Adipose tissues constitute a remarkably dynamic organ that is responsive to a range of stimuli from nutrients and hormones to external temperature. Brown and white adipose tissues (BAT and WAT) differ in their appearance and function. Whereas WAT is the primary site for lipid storage, BAT generates heat by oxidation of fatty acids to maintain body temperature. An additional adipocyte termed BRITE (brown-in-white or beige) is brown-like and found in WAT following beta adrenergic activation or cold exposure. White adipocytes contain a single lipid droplet (LD) occupying most of the cytoplasm (unilocular), while brown adipocytes are filled with many smaller LDs (multilocular) and contain many mitochondria. LD-associated proteins regulate the storage and release of lipids from LDs and are more highly expressed in BAT. We determined the differential gene expression profile of BAT and WAT depots and investigated the roles of key brown/BRITE adipocyte-enriched factors in lipid droplet (LD) biology and cell signalling. CIDEA is a marker of BAT and it coats the surface of LDs facilitating their enlargement. We have defined its mechanism of action and the discrete protein regions involved in: LD targeting, dimerization, LD clustering and lipid transfer. Furthermore, we identified an amphipathic helix which through binding of phosphatidic acid is required for LD enlargement. The physiological process of CIDE-dependent LD enlargement is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat. As with CIDEA, the G protein-coupled receptor Gpr120 is more highly expressed in BAT compared to WAT and is upregulated following cold exposure. The selective GPR120 agonist TUG-891 increases fat oxidation and reduces body weight and fat mass in mice. These effects coincide with decreased brown adipocyte lipid content and increased nutrient uptake by BAT. TUG-891 treatment of brown adipocytes in vitro induced O2 consumption, through GPR120-dependent and -independent mechanisms. TUG-891-activated GPR120 induced intracellular Ca2+ release, mitochondrial depolarization, and mitochondrial fission. GPR120 mediates anti-inflammatory effects and cross-talk between signalling pathways can modulate BAT function. Focusing on inflammatory pathways we found that treatment of brown adipocytes with lipopolysaccharide to activate TLR4 receptors profoundly affected adipocyte biology. The treatment stimulated the secretion of a wide range of cytokines and enhanced lipid storage. Analysis of transcriptional changes revealed upregulation of inflammatory mediators and downregulation of brown-fat associated genes coincident with reduced O2 consumption. The activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising strategy to increase lipid combustion and reduce obesity. Future strategies to activate or repress signaling pathways in BAT hold promise for new obesity treatments.