Abstract
Background/objectivesNumerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity.Subjects/methods143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points.ResultsCirculating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5–4.9) vs. 3.8 (3.2–4.6) µg/ml; p = 2.1 × 10−5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = −0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B.ConclusionsOur data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes.Trial registrationClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.
Highlights
Long-term success of dietary weight loss interventions is known to be limited by frequently observed body weight regain [1, 2]
Fetuin-B levels were associated with estimates of obesity, liver steatosis (HSI), and insulin resistance
HOMA-IR, low ISIClamp, and weaker insulin-mediated suppression of FFAs (FFASupp)) (Table 1). Some of these associations were found for Fetuin-A, no relationship was seen to estimates of obesity and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (Table 1)
Summary
Long-term success of dietary weight loss interventions is known to be limited by frequently observed body weight regain [1, 2]. Recent data indicate that especially adipose tissue function might represent a crucial element in this phenomenon [3]. Identification of molecular pathways regulating adipose function, with respect to adipose insulin sensitivity, may help to unveil the underlying mechanism involved in body weight regulation. Numerous cytokines produced in hepatocytes, myocytes, and adipocytes are involved in the inter-organ cross talk promoting a tissue-specific insulin efficacy [4, 5]. The hepatokine Fetuin-A inhibits insulin receptor tyrosine kinase [6] and is increased in the diabetic and prediabetic state as well as in liver steatosis [7, 8]. It was proposed to induce myocellular insulin resistance in humans [7] via TLR4 mediated adipose tissue inflammation [9]
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