Carbon monoxide reverses adipose tissue inflammation and insulin resistance upon loss of ovarian function

Abstract

We hypothesized that carbon monoxide (CO) might suppress chronic inflammation, which led to metabolic disturbances. Ovariectomy (OVX) was performed in mice to mimic chronic inflammation secondary to loss of ovarian function. OVX increased fat mass and the infiltration of highly inflammatory CD11c cells into adipose tissue (AT), resulting in a disturbance of glucose metabolism. Treatment of CO attenuated these; CO decreased recruitment of CD11c-expressing cells in AT and reduced expression of CD11c in bone marrow-derived macrophages, protecting them from M1 polarization. Upregulated cGMP and decreased reactive oxygen species were responsible for the inhibitory activity of CO on CD11c expression; knockdown of soluble guanylate cyclase or heme oxygenase-1 using small interfering RNAs reduced this inhibition substantially. Improved OVX-induced insulin resistance (IR) by CO was highly associated with its activity to attenuate AT inflammation. Our results suggest a therapeutic value of CO to treat postmenopausal IR by reducing AT inflammation.

Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

“…Recent findings have demonstrated that thermogenic capability sufficient to decrease body weight is induced by a specific stimulus in the process of WAT browning, in which the adipocytes are stimulated to upregulate typical genes of brown adipose tissue (BAT; Barbatelli et al, 2010). Since we and others have demonstrated that OVX increases fat mass, body weight, and metabolic rates without changes in food intake (Choi et al, 2014(Choi et al, , 2015Kim et al, 2013;Rogers et al, 2009), we hypothesized that OVX decreases browning in AT, leading to weight gain. OVX induced significant increases in body weight starting from 8 weeks after OVX, without any significant changes in food intake ( Figure 1a…”

“…Postmenopausal women experience various metabolic syndrome components including insulin resistance (Stefanska, Bergmann, & Sypniewska, 2015) and osteoporosis (Lorentzon, 2019). In animal models, ovariectomy (OVX) results in insulin resistance and fatty liver, with increased visceral fat and chronic inflammation (Choi et al, 2015; Kim et al, 2013; Rogers, Perfield 2nd, Strissel, Obin, & Greenberg, 2009), and exhibits a pattern of pathogenesis similar to diet‐induced obesity (DIO). The development of pathogenesis in DIO has been reported to be caused by increased fat mass, leading to the accumulation of adipose tissue macrophages (ATMs) that actively participate in chronic inflammation (Lumeng, Bodzin, & Saltiel, 2007).…”

Hydrogen Sulfide in the Adipose Tissue—Physiology, Pathology and a Target for Pharmacotherapy

“…In addition, adipose tissue produces classic cytokines (tumor necrosis factor-α, TNF-α, interleukin-6), chemokines (interleukin-8, monocyte chemoattractant protein-1, MCP-1), hormones (angiotensin II, adrenomedullin, atrial natriuretic peptide), growth factors, enzymes and enzyme inhibitors (visfatin, vaspin, plasminogen activator inhibitor-1) and acute phase proteins. Adipose tissue secretes also non-protein biologically active mediators including gasotransmitters (NO, CO and H 2 S) [ 21 , 22 , 23 , 24 , 25 ].…”

Hepatic miR‐125b inhibits insulin signaling pathway by targeting PIK3CD

“…Globally, it is expected to afflict around 500 million people by 2030 (Gustafson, Hedjazifar, Gogg, Hammarstedt, & Smith, ). Although several mechanisms, including inflammation (Choi et al, ), oxidative stress, and mitochondrial dysfunction (Wright et al, ), have been reported to be involved in insulin resistance, the molecular underpinnings of insulin resistance and insulin signaling impairments are only partially understood.…”