Adipose tissue distribution is a key determinant of metabolic health and cannot be fully explained by total fat mass or body mass index alone. Major adipose compartments, including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thermogenic brown and beige adipose tissues, and ectopic lipid accumulation in non-adipose organs, differ markedly in cellular composition, developmental origin, endocrine function, inflammatory status, and metabolic activity. Excess visceral and ectopic fat is strongly associated with insulin resistance, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), metabolic syndrome (MetS), and organ-specific metabolic injury, whereas lower-body SAT may provide a relatively safe lipid-buffering reservoir. Advances in imaging, body-composition analysis, functional metabolic assessment, single-cell omics, and genetic studies have refined the characterization of adipose tissue distribution and its regulatory basis. Current evidence indicates that regional fat patterning is governed by integrated adipogenic, thermogenic, developmental, endocrine, genetic, and environmental programs, and is further modified by sex, age, ethnicity, diet, physical activity, sleep, and stress. Therapeutic strategies also differ substantially in their effects on adipose distribution. Lifestyle intervention and glucagon-like peptide-1 receptor agonists mainly reduce visceral and ectopic fat alongside overall weight loss, thiazolidinediones (TZDs) more directly reshape lipid partitioning, and thermogenic approaches such as cold exposure and β3-adrenergic stimulation remain biologically attractive but not yet established for routine clinical use. Rather than treating adipose depots as isolated anatomical compartments, this review proposes an integrated framework linking depot-specific biology, lipid-buffering capacity, clinical assessment, and therapeutic remodeling. This framework highlights the need for standardized depot-specific phenotyping and precision therapies that target metabolically harmful fat distribution rather than total adiposity alone.
