Metabolic impairment induces a state of low-grade inflammation triggering cardiovascular dysfunction. In parallel, western-type diets drive an imbalance of microorganisms in the gut known as dysbiosis. Recent research implicates localized inflammation in certain adipose depots in causing the earliest pathologies in cardiovascular tissues/organs. Dysbiosis was suggested to augment the inflammatory phenotype in adipose tissue, increasing the risk of cardiovascular disease. Here, we describe the early molecular changes in these adipose depots, demonstrate the pathways through which microbiota alters the host mitochondria, causing the observed alterations, and highlight the sex-based differences in these cascades. Potential therapies modulating these processes are discussed.