Abnehmen bei Insulinresistenz: Muskel-Typ oder Leber-Typ entscheidet mit

<h4>Objective</h4>We previously identified distinct muscle and liver insulin resistance (IR) metabotypes in middle-aged and older adults. The PERSON study showed that a low-fat, high-protein, high-fiber diet benefits the muscle IR group, while a high-monounsaturated fatty acid diet benefits the liver IR group. We also developed the MetaboHealth score, reflecting risks of mortality, frailty, and cognitive decline. This study aimed to examine whether MetaboHealth interacts with IR metabotypes to influence (i) cardiometabolic health and (ii) body composition outcomes in the PERSON study, informing precision nutrition strategies.<h4>Methods</h4>In total, 242 adults aged 40-75 with IR were randomized to follow an isocaloric low-fat, high-protein, high-fiber or high-monounsaturated fatty acid diet for 12 weeks. Of these, 184 with complete data were grouped into MetaboHealth tertiles (higher = poorer health). Outcomes included a 7-point oral glucose tolerance test and DXA-based body composition. Linear mixed models assessed four-way interactions.<h4>Results</h4>No interaction was observed for cardiometabolic outcomes. Significant interactions were found for android, gynoid, total fat percentage, and fat mass index. In the healthiest tertile, matched diets led to greater fat loss. In the poorest tertile, both diets were similarly effective. MetaboHealth remained unchanged.<h4>Conclusions</h4>Combining metabotype with MetaboHealth may enhance personalized dietary strategies for fat lo

The influence of protein intake on insulin resistance, has garnered an increasing amount of interest over the past few decades. Increased provisions of dietary protein during weight loss helps preserve skeletal muscle, which as the largest organ in the human body, is responsible for 80% of insulin-stimulated glucose disposal. The postprandial influence of essential amino acids (EAAs) either alone or as part of intact proteins are regulated through leucine-induced activation of mammalian target of rapamycin (mTOR) that serves to promote muscle protein synthesis and maintain skeletal muscle. High protein diets and/or EAA supplementation have also been demonstrated to improve satiety and augment mitochondrial function, which may have an indirect or direct influence on insulin sensitivity. On the other hand, chronic elevations in postabsorptive concentrations of branched chains amino acids (BCAAs) have been associated with chronic activation of the mTOR pathway, impairing insulin action. It appears that causal links between BCAAs and the pathogenesis of insulin resistance are reliant on chronic hyperinsulinemia and nutrient overload that foster chronic lipotoxicity. Conversely, postprandial elevations in EAAs leverage sensing as an anabolic mediator to facilitate muscle remodeling, augment satiety and improve metabolic regulation.

Insulin resistance develops when skeletal muscle (SM), adipose tissue (AT), and the liver fail to respond adequately to insulin, a dysfunction closely intertwined with chronic low-grade inflammation. This combination leads to compensatory hyperinsulinemia, dysglycemia, and metabolic stress, driving major disorders such as type 2 diabetes, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease. Both adipokines and myokines are central modulators of this metabolic-inflammatory axis. In obesity, diabetes, MASLD, and thyroid dysfunction, alterations in myokines such as myostatin, irisin, fibroblast growth factor 21 (FGF-21), apelin, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-15 (IL-15) influence glucose uptake, lipid oxidation, mitochondrial function, and systemic inflammation. Exercise-induced myokines exert insulin-sensitizing and anti-inflammatory effects, whereas myostatin and tumor necrosis factor-alpha (TNF-α) promote metabolic impairment. These pathways reveal extensive crosstalk between SM and key metabolic organs-including the liver, pancreas, AT, intestine, heart, and thyroid gland. In metabolic disease, inflammation-driven changes in deiodinase activity and triiodothyronine (T3) availability further link muscle dysfunction with thyroid imbalance. The aim of this narrative review was to elucidate the complex interplay between myokines, adipokines, inflammation, and insulin res