Normalization of adiponectin concentrations by leptin replacement in ob/ob mice is accompanied by reductions in systemic oxidative stress and inflammation

Abstract

The circulating concentrations of adiponectin, an antidiabetic adipokine, have been shown to be reduced in obesity, in relation to an increase in inflammation. The aim of the present work was to assess the effect of leptin replacement on adiponectin levels and expression as well as on markers of oxidative stress and inflammation in leptin-deficient ob/ob mice. Twelve-week-old male mice (n = 7–10 per group) were treated with either saline (wild type and ob/ob mice) or leptin (ob/ob mice) for 18 days. A third group of ob/ob mice was treated with saline and pair-fed to the amount of food consumed by the leptin-treated group. Leptin replacement restored values of adiponectin (P < 0.001), reduced circulating 8-isoprostane and serum amyloid A (SAA) levels (P < 0.05 for both), and significantly downregulated the increased gene expression of osteopontin (Spp1, P < 0.05), Saa3 (P < 0.05), Cd68 (P < 0.01), Il6 (P < 0.01) and NADPH oxidase (Nox1 and Nox2, P < 0.01) in the perirenal WAT and Spp1 (P < 0.05) in the liver of ob/ob mice. In cultured adipocytes from ob/ob mice, leptin increased (P < 0.05) the mRNA expression and secretion of adiponectin. We concluded that circulating concentrations of adiponectin are positively regulated by leptin and ameliorate obesity-associated oxidative stress and inflammation in mice.

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

“…Interestingly, CCK‐8 apparently promoted an anti‐inflammatory response as it tended to repress the expression of the pro‐inflammatory cytokines IL‐6, IL‐1β, and TNF‐α in both Sc‐WAT and Vis‐WAT (see Figure S2). This effect would be consistent with the known anti‐inflammatory effect of adiponectin (Frühbeck et al, ) and could contribute to an improvement in insulin sensitivity (Blüher, ).…”

“…In any case, it has to be noted that the inhibition of food intake, together with the decrease of body weight triggered by CCK‐8 (Plaza, Merino, Cano, et al, ), might contribute to the increase of adiponectin plasma levels (Reinehr, Roth, Menke, & Andler, ). At this point, it has to be highlighted that chronic CCK‐8 led to a decrease of leptin plasma levels (Plaza, Merino, Cano, et al, ) that would rather limit the effect of CCK‐8 on Adipoq expression, as leptin has been shown to induce the expression of adiponectin (Frühbeck et al, ; Singh et al, ). A relevant circumstance that deserves attention is the fact that the effect of CCK‐8 on Adipoq expression seems to be slightly more intense in Sc‐WAT than in Vis‐WAT.…”

Taste Receptor Cells in Mice Express Receptors for the Hormone Adiponectin

“…As expected, plasma and saliva samples from APN KO mice were negative for adiponectin (Figure 9C). Mice receiving the AAV5-APN-miR vector show diminished circulating levels of adiponectin (11.66 ± 10.32 ng/ml; Figure 9A), approximately 1000-fold less than seen in WT mice (6.088 μg/ml; Figure 9C) and less likely to have a biological impact (Frühbeck et al . 2017).…”

“…By targeting expression to just the salivary glands, salivary adiponectin expression reached wildtype levels while circulating adiponectin levels were 1000-fold less than those in a WT mouse (Frühbeck et al . 2017). However, we were unable to completely limit adiponectin expression to either blood or saliva in either rescue model.…”

Acute physical exercise increases the adaptor protein APPL1 in the hypothalamus of obese mice

“…Also, APPL1 can prevent Akt from being inactivated by the TRB3 protein [12]. Furthermore, obesity is associated with a reduction in serum adiponectin levels, in the AdipoR1 (adiponectin 1 receptor) as well as in the APPL1 protein content in peripheral tissues [13][14][15]. On the other hand, APPL isoform 2 (APPL2) performs a counteraction in APPL1 regulation [6].…”