Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer

Abstract

BackgroundCancer cachexia is a multifactorial metabolic syndrome characterized by marked loss of adipose tissue and skeletal muscle. Fat loss from adipose tissue in cancer cachexia is partly the result of increased lipolysis. Despite the growing amount of studies focused on elucidating the mechanisms through which lipolysis-related proteins regulate the lipolytic process, there are scarce data concerning that profile in the adipose tissue of cancer cachectic patients. Considering its fundamental importance, it was our main purpose to characterize the expression of the lipolysis-related proteins in the white adipose tissue of cachectic cancer patients.MethodsPatients from the University Hospital were divided into three groups: control, cancer cachexia (CC), and weight-stable cancer patients (WSC). To gain greater insight into adipose tissue wasting during cancer cachexia progression, we have also analyzed an experimental model of cachexia (Walker 256 carcinosarcoma). Animals were divided into: control, intermediate cachexia (IC) and terminal cachexia (TC). Subcutaneous white adipose tissue of patients and epidydimal white adipose tissue of animals were investigated regarding molecular aspects by determining the protein content and gene expression of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), perilipin 1, leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha).ResultsWe found augmented lipolysis in CC associated with increased HSL expression, as well as upregulation of ATGL expression and reduction in perilipin 1 content. In IC, there was an imbalance in the secretion of pro- and anti-inflammatory factors. The alterations at the end-stage of cachexia were even more profound, and there was a reduction in the expression of almost all proteins analyzed in the animals.ConclusionsOur findings show that cachexia induces important morphological, molecular, and humoral alterations in the white adipose tissue, which are specific to the stage of the syndrome.

Adipose Tissue Remodeling during Cancer Cachexia

“…Interestingly, the tumor-bearing animals exhibited a reduction in basal lipolysis 4 days after inoculation, while on Day 14, the cachectic animals exhibited a considerable increase in the basal lipolysis rate ( Figure 1B). These findings corroborate with the results of other studies showing increased lipolysis in the subcutaneous AT of cachectic patients [9,51].…”

Dropping in on lipid droplets: insights into cellular stress and cancer

“…It was recently proposed that chemotherapy-induced cachexia is driven by oxidative stress-associated MAPK activation in mitochondria of muscle tissues, as in the case of Folfox or Folfiri drug treatments [ 192 ]. Elevated levels of plasma FFAs, TG and cholesterol correlate with muscle and adipose tissue wasting in cancer patients with cachexia [ 193 ]. Moreover, expression levels of LD-associated proteins are altered in cancer-associated cachexia resulting in changes in adipocyte morphology.…”

“…WAT characteristically stores a single oversized LD for energy storage that occupies the bulk of the cytoplasm, while brown adipose tissue (BAT) contains small LDs and an unusually high abundance of mitochondria consequently releasing heat through FA β-oxidation [ 195 ]. Increased lipolysis in WAT is also modulated by HSL [ 193 , 196 ]. Although lipid breakdown is the major determinant of cancer cachexia, impaired lipogenic and lipid storage pathways have been closely associated with adipose tissue atrophy [ 197 ].…”

Immunometabolism features of metabolic deregulation and cancer

“…Increased immune cells presence in WAT of CC patients, 96 is one of the evidence that how metabolic states in cancer are affected by Immunometabolism. Similar findings were expressed in mice.…”

“…Cancer cachexia (CC) is a complex wasting syndrome associated to the majority of cancers, and characterised by abnormal immune cells activation and their presence in metabolic tissues. Increased immune cells presence in WAT of CC patients, is one of the evidence that how metabolic states in cancer are affected by Immunometabolism. Similar findings were expressed in mice .…”