Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Abstract

Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma -6/-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.

Ileal interposition surgery targets the hepatic TGF‐β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD‐T2DM rat model of diabetes

“…S13) in any of the enzymatic activities tested (including CCO). This indicated that IT surgery is likely to have a relatively short-term effect (14) as we previously reported for endoplasmic reticulum stress response mitigation and adipose tissue remodeling after IT surgery (11).…”

“…Recently, we reported that IT surgery had a more profound and prolonged effect on mesenteric fat depot than the other adipose depots that were studied (inguinal, epididymal, or retroperitoneal) (11). This specific effect on mesenteric adipose tissue was associated with changes that would be expected to ensue in a delay in the maturation of adipocytes (11).…”

“…These included increased circulating bile (cholic) acid levels, which we postulated to explain the decreased endoplasmic reticulum stress and inflammation; the improvement of insulin signaling in adipose, liver, skeletal muscle and pancreas; and the enhanced glucose-stimulated insulin secretion and preservation of islet integrity and b-cell mass following IT surgery (8,14,35). Recently, we reported that IT surgery had a more profound and prolonged effect on mesenteric fat depot than the other adipose depots that were studied (inguinal, epididymal, or retroperitoneal) (11). This specific effect on mesenteric adipose tissue was associated with changes that would be expected to ensue in a delay in the maturation of adipocytes (11).…”

“…To assess early changes mediated by IT surgery on bioenergetics, we studied male rats (2 mo of age at the time of surgery), 1.5 mo postsurgery because at this time point ( Fig. 1 indicated with an arrow), none of the animals that underwent either IT or sham surgery had developed diabetes (11,14). Hepatic gene expression obtained at 1.5 mo post-IT surgery vs. sham surgery indicated a total of 2807 genes were differentially expressed, with the majority of them being down-regulated (2074 or 74% of the total; Fig.…”

RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis

“…Adipose tissues are known to preserve food-derived lipids as excess energy and function as an endocrine organ for energy homeostasis by secreting related hormones [ 1 ]. Dysfunction of the physiological roles of adipose tissues occurs with an expanded mass of white adipocytes (WAs) that subsequently induce human obesity [ 2 ]. In contrast, brown adipocytes (BAs) were discovered to execute non-shivering thermogenesis by dissipating stored lipid droplets in small rodents and infants [ 3 ].…”