Among healthy Japanese men without obesity, reduced adipose tissue insulin sensitivity was associated with liver fat accumulation, lower insulin clearance, muscle insulin resistance and increased risk for dyslipidemia, according to findings from a prospective study.
“Research has suggested that adipose tissue insulin resistance is induced by obesity and is the result of the reduced ability of subcutaneous adipose tissue to store lipids,” Yoshifumi Tamura, MD, PhD, an associate professor in the department of metabolism and endocrinology at Juntendo University Graduate School of Medicine in Tokyo, told Endocrine Today. “Then lipid spillover promotes visceral and ectopic fat accumulation and insulin resistance. Surprisingly, our data suggested that even in non-obese, apparently healthy Japanese men, lipid spillover is already observed, and it is associated with clinical features of metabolic syndrome. This phenomenon may be involved in the mechanisms why Asians readily develop metabolic disease, even in the absence of obesity.”
Tamura and colleagues analyzed data from 52 Japanese men aged 30 to 50 years without obesity and no cardiometabolic risk factors participating in the Sportology Center Core Study, a prospective, observational study assessing underlying mechanisms of metabolic abnormalities in people without obesity (mean age, 41 years; mean BMI, 23.1 kg/m²). All men underwent an oral glucose tolerance test and peak oxygen uptake test at baseline screening. Researchers measured insulin sensitivity in muscle, liver and adipose tissue using a two-step hyperinsulinemic-euglycemic clamp with glucose tracer after an overnight fast. Adipose tissue insulin sensitivity was calculated as percent free fatty acid suppression/insulin concentration during the first step of the glucose clamp process. Based on the median adipose tissue insulin sensitivity value, researchers stratified men into low (n = 26) and high (n = 26) free fatty acid suppression groups.
Researchers found that men in the low free fatty acid suppression group had moderate fat accumulation in abdominal subcutaneous adipose tissue and in the liver. When compared with men in the high free fatty acid suppression group, men in the low-level group also had a lower fitness level, decreased insulin clearance (mean fasting serum insulin, 6.1 vs. 3.8 µU/mL), impaired insulin sensitivity in muscle and moderately elevated triglyceride levels (mean, 121.7 vs. 89.4 mg/dL; P = .011), as well as lower HDL cholesterol levels (mean, 54.2 vs. 63.1 mg/dL; P = .015).
Hepatic insulin sensitivity was similar between groups, according to researchers; however, basal endogenous glucose production was lower in the low free fatty acid suppression group, likely due to higher insulin levels.
In correlation analyses, researchers found that free fatty acid suppression was positively associated with percent body fat and subcutaneous fat area, but not visceral fat area. Additionally, insulin sensitivity in the muscle, but not in the liver, was correlated with percent of free fatty acid suppression; however, free fatty acid suppression was not correlated with age, free fatty acid level, area under the curve during the OGTT or daily physical activity level.
“Clinicians should take note of even small weight gain in healthy Asians, because lipid spillover could occur in this healthy population and facilitate further metabolic disorder,” Tamura said. “We recently defined ‘metabolic gradation’ as the gradual transition from an insulin-sensitive to an insulin-resistant state. Adipose tissue insulin resistance may be an early change that drives subsequent metabolic disorders.” – by Regina Schaffer
For more information:
Yoshifumi Tamura, MD, PhD, can be reached at Juntendo University Graduate School of Medicine, Department of Metabolism & Endocrinology, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; email: firstname.lastname@example.org.
Disclosures: The authors report no relevant financial disclosures.