Increased recruitment of brown adipose tissue has been reported to occur during hyperphagia and chronic cold exposure in animal models. However, few studies have focused on the investigation of this phenomenon in humans. We studied patients with a mitochondrial encephalopathy, Myoclonic Epilepsy with Ragged Red Fibres (MERRF) who develop large masses of adipose tissue known as lipomas specifically in the interscapular, subscapular and cervical regions. These patients harbour a single nucleotide substitution (m.8344A>G) within the mitochondrial genome and develop neurological features such as dementia, ataxia and myoclonic jerks. We have established that lipomas consist of brown adipose tissue which contains high levels of mutant mtDNA and are significantly deficient in key mitochondrial respiratory chain subunits. Proliferating adipocytes were found in lipomas based on Ki67 protein expression and increased macrophage infiltration was detected by CD68 immunohistochemistry suggesting that cellular hypertrophy and hyperplasia are involved in tissue expansion. We propose that the lack of functional respiratory chain subunits hinders uncoupling by UCP1 leading to the generation of a negative feedback loop to increase recruitment of brown adipose tissue. Increased recruitment of brown adipose tissue was investigated by studying the cAMP-PKA signalling pathway in lipoma tissues. An upregulation of β3 adrenergic receptors, along with the detection of P-CREB exclusively in patient tissues and preferential expression of PGC1α was indicative of increased cAMP-PKA signalling involved in lipoma formation. The main aim of this work is to develop treatment strategies to prevent the formation of these disfiguring and uncomfortable lipomas in patients harbouring the m.8344A>G mutation.