Trehalose Prevents Adipocyte Hypertrophy and Mitigates Insulin Resistance in Mice with Established Obesity

Abstract

Summary Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/ HFD group were significantly lower than those in the DW/HFD group (p,0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.

Daily Intake of Trehalose Is Effective in the Prevention of Lifestyle-Related Diseases in Individuals with Risk Factors for Metabolic Syndrome

“…Using a metabolic syndrome mouse model, we have previously shown that trehalose intake mitigates insulin resistance and decreases impaired glucose tolerance as assessed using OGTT, and these effects are attributed to the suppression of adipocyte hypertrophy (2,3). In this study, to assess the preventive effect of trehalose on the development of metabolic syndrome, we examined whether this disaccharide suppresses the progression of insulin resistance in humans.…”

“…These effects were also evident in an established obese mouse model when 0.3% (weight/volume) trehalose was consumed via its addition to drinking water (3). The effective dose was 0.2 g/kg of body weight/d and translated to 10 g/d in humans weighing 50 kg (3). Thus, these findings suggested that ingestion of 10 g/d trehalose is effective for reducing the risk of onset of metabolic syndrome in humans.…”

“…Our previous studies on metabolic syndrome using a mouse model showed that trehalose intake in mice fed with a high-fat diet (HFD) suppressed mesenteric adipocyte hypertrophy and decreased impaired glucose tolerance in an oral glucose tolerance test (OGTT) (2). In the mice fed with HFD, we also found that trehalose intake mitigated insulin resistance, reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) (2), and increased serum high molecular weight (HMW) adiponectin (3). These effects were also evident in an established obese mouse model when 0.3% (weight/volume) trehalose was consumed via its addition to drinking water (3).…”

“…In the mice fed with HFD, we also found that trehalose intake mitigated insulin resistance, reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) (2), and increased serum high molecular weight (HMW) adiponectin (3). These effects were also evident in an established obese mouse model when 0.3% (weight/volume) trehalose was consumed via its addition to drinking water (3). The effective dose was 0.2 g/kg of body weight/d and translated to 10 g/d in humans weighing 50 kg (3).…”

Inkjet printing of insulin microneedles for transdermal delivery

“…However, studies using mouse models have found that trehalose suppresses adipocyte hypertrophy and mitigates insulin resistance. This could be a cause for concern, as a resistance of the delivered insulin would undermine the stabilizing properties of the polymer [17]. Another potential stabilizer analysed is polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®).…”