Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes

Abstract

Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin.Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone-and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model.

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

“…The similar plasma NEFA concentration between STZ rats and controls may be explained by the depleted lipid stores in the adipose tissue. In accord with this, the EWAT content of STZ rats represented only ϳ0.3% of the animals' body weight compared with 0.6 -1.2% reported for healthy controls (11,58,66).…”

Neonatal streptozotocin-induced diabetes in mothers promotes metabolic programming of adipose tissue in male rat offspring

“…This model also exhibits insulin resistance, hypoadiponectinemia and hypoleptinemia in adulthood, as demonstrated by previous studies published by our group (Takada et al, 2007;Oliveira et al, 2012;Takada et al, 2008).…”

Metabolic adaptations in the adipose tissue that underlie the body fat mass gain in middle-aged rats

“…Hypothetically, directing these substrates to the adipose tissue results in initial benefits for two reasons: first, it prevents the increase in glycemia and lipidemia, which brings toxicity and metabolic dysfunction to other tissues; and second, because there is a very large capacity for storing these substrates in the form of triglycerides, adipose tissue works as a metabolic buffer that prevents the potentially harmful effects of lipotoxicity caused by ectopic fat accumulation. In this sense, metabolic adipose tissue recovery (induced by the PPARγ agonist Pioglitazone) is associated with a better improvement in an experimental model of streptozotocin-induced diabetes than drugs which does not induce adipose metabolic recovery (Takada et al 2008). Still, in a transgenic model of increased PEPCK enzyme, in which an increased re-esterification of fatty acids occurs due to the greater availability of glycerol synthesized from substrates such as lactate, obesity is induced; however, it is exempted from insulin resistance (Franckhauser et al 2002).…”