Movement appears more crucial for certain insulin-resistant individuals (including myself) due to our genes. Movement does not need be structured or scripted activity. All physical movement in essence is effective. This includes housekeeping, car washing, hunting/gathering... (even s..e..x..) counts. And movement appears to defy physics. The more movement engaged... and the more intense... the less effort later. (???!) Is that like life? The more we love 'n give... the more we l-i-v-e?
Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. Thamer C, et al. J Clin Endocrinol Metab. 2008 Apr;93(4):1497-500.
CONTEXT: We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI).
OBJECTIVE: The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI.
DESIGN: A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging.
RESULTS: With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles.
CONCLUSION: SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes. PMID: 18252792
All the PPAR receptors have similar ligands -- endogenous and exogenous fatty acids (short-chain, medium-chain, long-chain, MUFA, PUFA, SFA, etc) and eicosanoids (steroidal products from the prostaglandin cascade, including COX derivatives). They truly are pivotal controllers when all lifestyle and nutritional factors are optimized. Although such a wide-range of substances can bind and activate these receptors, Amino Acids (via the mTOR pathway) appear to be one the most potent stimulators of PPAR. Amino Acid sufficiency can determine and maximize all the functions of PPAR-Gamma (and Alpha and Delta) -- metabolism, maintenance and synthesis of muscle fibers, thermogenesis, burning fat, storing fat, and the overall balancing of energy. Not only can PPARs regulate diabetes/insulin resistance and heart disease, but with their optimization of function, PPARs can also reverse these conditions. PPARs ameliorate atherosclerosis. Both food and omega-3 trials and drug (alpha, gamma, delta) trials demonstrate this already.
Don't be sarcopenic... Build a wealth of heart protection in your flesh. How much meaningful movement do you have in your daily life?
Regulation of peroxisome proliferator-activated receptor-gamma activity by mammalian target of rapamycin and amino acids in adipogenesis. Kim JE, Chen J. Diabetes. 2004 Nov;53(11):2748-56.
Adipocyte differentiation is a developmental process that is critical for metabolic homeostasis and nutrient signaling. The mammalian target of rapamycin (mTOR) mediates nutrient signaling to regulate cell growth, proliferation, and diverse cellular differentiation. It has been reported that rapamycin, the inhibitor of mTOR and an immunosuppressant, blocks adipocyte differentiation, but the mechanism underlying this phenomenon remains unknown. Here we show that mTOR plays a critical role in 3T3-L1 preadipocyte differentiation and that mTOR kinase activity is required for this process. Rapamycin specifically disrupted the positive transcriptional feedback loop between CCAAT/enhancer-binding protein-alpha and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), two key transcription factors in adipogenesis, by directly targeting the transactivation activity of PPAR-gamma. In addition, we demonstrate for the first time that PPAR-gamma activity is dependent on amino acid sufficiency, revealing a molecular link between nutrient status and adipogenesis. The results of our further investigation have led us to propose a model in which the mTOR pathway and the phosphatidylinositol 3-kinase/Akt pathway act in parallel to regulate PPAR-gamma activation during adipogenesis by mediating nutrient availability and insulin signals, respectively. It is interesting that troglitazone (a thiazolidinedione drug WHICH BINDS PPAR-Gamma) reversed the inhibitory effects of rapamycin and amino acid deprivation, implicating therapeutic values of thiazolidinedione drugs to counter certain side effects of rapamycin as an immunosuppressant. PMID: 15504954
(Diagram from here; Williamson DL, et al. Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. J Physiol. 2006 June 1; 573(Pt 2): 497–510. )