Metabolic and histomorphological changes of adipose tissue in cachexia

Abstract

Purpose of reviewTo describe the role of the main changes occurring in adipose tissue during cachexia and how these affects patient's outcomes, with a specific focus on cancer.Recent findingsIn cachexia, the changes within the adipose tissue have been recently described as the presence of inflammatory infiltration (T-lymphocytes and macrophages), enhanced fibrosis, and the occurrence of beige adipocytes (i.e., browning). The latter one is a process driving cachexia enhancing thermogenesis, primarily via modulation of uncoupling protein 1. Also, increased lipolysis of white adipose tissue, especially in cancer, via higher expression of hormone sensible and adipose tissue triglyceride lipases, was detected in experimental models and in human adipose tissue. Other systemic metabolic alterations occur in association with changes in adiposity, including insulin resistance and increased inflammation, all conditions associated with a worse outcome. Moreover, these profound metabolic alterations were shown to be implicated in several consequences, including extreme and progressive unvoluntary body weight loss.SummaryAlterations in adiposity occur early during cachexia. Adipose tissue atrophy, as well as metabolic changes of white adipose tissues were observed to be pivotal in cachexia, and to be implicated in several clinical complications and poor prognosis.Further research is necessary to clarify the mechanisms underlying the loss of adiposity and therefore to identify novel therapeutic options to counteract this phenomenon in cachexia.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer

“…This was also documented for the expression of PPAR α documenting a trend of its increase in the same cohort . In this regard, data available in the literature indicate that adipose tissue loss is a common feature in cancer cachexia and is in part the result of deep changes in the balance of energy storage and mobilization of fat tissue [ 4 , 15 ].…”

“…We believe that the information given by our study is of interest because it integrates the understanding of the mechanisms of lipolysis associated with adipose tissue loss in cancer since the early clinical presentation of the disease in association with other clinically relevant phenomena, including adipose tissue fibrosis, inflammatory infiltration, as well as browning process [ 4 , 6 ]. In fact, the molecular brakes of adiposity are complex and not yet clarified especially in humans, and in particular during the cancer journey.…”

“…During cancer, several metabolic alterations occur and lead to peripheral tissue abnormalities, mainly represented by muscle and adipose tissue atrophy [ 1 , 2 ]. Importantly, both loss of muscularity and adipose tissue have been shown to significantly impact clinical outcomes among cancer patients [ 3 , 4 ].…”