Alterations in adipose tissue during critical illness: an adaptive and protective response?

Endocrine, Metabolic, and Morphologic Alterations of Adipose Tissue During Critical Illness*

“…We recently demonstrated profound alterations in morphology of adipose tissue during critical illness ( Figure 1). In a rabbit model of prolonged illness, we demonstrated a decrease in median adipocyte cell size with time, whereas the total weight of the isolated fat pad did not change, together pointing to an increase in adipocyte cell number (18). This observation was confirmed in adipose tissue biopsies of critically ill patients (18).…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…Insulin acts also via an Akt-Independent PI3K-dependent signalling pathway which modifies PKA phosphorylation of perilipin [91]. The reduction in insulin activity is responsible for increased lipolysis in diabetes and obesity together with the reduction in the insulinsensitizing activity of adiponectin [92] probably linked to the adipose tissue dysfunction described in sepsis [17,18]. Moreover adiponectin may reduce fat deposition in visceral adipose tissue increasing the deposit in the subcutaneous compartment through PPAR upregulation [18].…”

“…The reduction in insulin activity is responsible for increased lipolysis in diabetes and obesity together with the reduction in the insulinsensitizing activity of adiponectin [92] probably linked to the adipose tissue dysfunction described in sepsis [17,18]. Moreover adiponectin may reduce fat deposition in visceral adipose tissue increasing the deposit in the subcutaneous compartment through PPAR upregulation [18]. The lipolytic activity is differently regulated in subcutaneous and visceral fat: the former, more important for the basal activity, is more sensitive to the antilipolytic action of insulin, the latter is mainly activated during hormonal stimulation and provides FFA directly to the liver through the portal circulation in physiological and pathophysiological situations.…”

“…The lipolytic activity is differently regulated in subcutaneous and visceral fat: the former, more important for the basal activity, is more sensitive to the antilipolytic action of insulin, the latter is mainly activated during hormonal stimulation and provides FFA directly to the liver through the portal circulation in physiological and pathophysiological situations. In sepsis seems to be present a failure of adipocytes differentiation leading to a decreased storage ability of the subcutaneous tissue allowing FFA to be accumulated in visceral fat (with an increase in the metabolic and cardiovascular risk) and in organs giving rise to lipotoxicity for the concomitant reduction of FAO [18]. Lipolysis is increased in sepsis [14] due to a raised activity of the lipases of the adipose tissue, mainly the HSL, because of the increased plasma level of catecholamines, ILs and natriuretic peptides and the reduced activity of insulin and adiponectin (fig 3).…”

“…because they mediate the inflammatory reaction to the alarmins released by these noxae: the deletion of TLR2 and TLR4 may reduce the cellular damage in these settings [13][14].The mitochondrial DNA released after tissue damage may be recognized by TLRs, behaving as a DAMP for its far origin by bacteria according to endosymbiotic theory; its experimental infusion may cause a picture similar to the ARDS [15]. TLRs are also important to explain the link between inflammation and metabolic alterations [16] and the state of low grade inflammation present for so far unknown reasons in obesity, metabolic syndrome, diabetes and in chronic myocardial ischemia; moreover they may also be involved in the adipose tissue dysfunction described during sepsis [17,18]. One of the main problems in the study of sepsis has been its experimental reproduction: the LPS infusion method, used also at low doses in human volunteers, is not reliable because it reproduces only the proinflammatory phase and led in the past to misunderstand the complex regulation of immunity in sepsis, moreover in this model is lacking an infectious focus.…”