Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype?

Abstract

LPL is an enzyme involved in the breakdown and uptake of lipoprotein triglycerides. In the present study, we examined how the transgenic (Tg) overexpression of human LPL in mouse skeletal muscle affected tolerance to cold temperatures, cold-induced thermogenesis, and fuel utilization during this response. Tg mice and their nontransgenic controls were placed in an environmental chamber and housed in metabolic chambers that monitored oxygen consumption and carbon dioxide production with calorimetry. When exposed to 4jC, an attenuation in the decline in body temperature in Tg mice was accompanied by an increased metabolic rate (15%; P , 0.001) and a reduction in respiratory quotient (P , 0.05). Activity levels, the expression of uncoupling proteins in brown fat and muscle, and lean mass failed to explain the enhanced cold tolerance and thermogenesis in Tg mice. The more oxidative type IIa fibers were favored over the more glycolytic type IIb fibers (P , 0.001) in the gastrocnemius and quadriceps muscles of Tg mice. These data suggest that Tg overexpression of LPL in skeletal muscle increases cold tolerance by enhancing the capacity for fat oxidation, producing an avian-like phenotype in which skeletal muscle contributes significantly to the thermogenic response to cold temperatures.-Jensen, D. R., L. A. Knaub, J. P. Konhilas, L. A. Leinwand, P. S. MacLean, and R. H. Eckel. Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype? J. Lipid Res. 2008. 49: 870-879.

Exercise reduces appetite and traffics excess nutrients away from energetically efficient pathways of lipid deposition during the early stages of weight regain

“…Obesity-resistant rats respond to overfeeding, in part, by increasing TEE and the oxidation of dietary fat (32,33), and regular exercise adjusts the relapse-associated overfeeding response in a similar manner. These adaptations enhance the response to other metabolic challenges as well (27,51), Increasing skeletal muscle oxidative capacity with the overexpression of LPL, rather than with regular exercise, yields a similar improvement in the metabolic response to cold exposure (37). Even so, most of the exercise-induced changes in gene expression are eliminated by overfeeding on the first day of relapse (Fig.…”

Mice lacking G0S2 are lean and cold-tolerant

“…24 In addition, overexpression of lipoprotein lipase in skeletal muscle enhanced cold tolerance by shifting the muscle fiber type toward the more oxidative type IIa and increasing fat oxidization capability. 25 Muscle activity was also thought to be enhanced with increased mitochondria content and increased total ATP capacity in UCP-1 knockout mice. 26 Therefore, although we did not observe changes in shivering of G0S2 −/− mice, it is possible that G0S2 −/− mice have enhanced heat generation in their muscles as compared with G0S2 +/+ mice.…”

Skin-specific Deletion of Stearoyl-CoA Desaturase-1 Alters Skin Lipid Composition and Protects Mice from High Fat Diet-induced Obesity

“…Organisms have developed a variety of ways to sacrifice fuel efficiency to maintain temperature homeostasis, one of which is the uncoupling of respiration from ADP phosphorylation via mitochondrial UCPs (73). UCP-1 in BAT of rodents is robustly induced in response to cold, and it has been established as an important regulator of temperature and energy homeostasis (50,51,71,74). Additionally, uncoupling in other tissues such as skeletal muscle via UCP-2 and -3 also contributes to the thermogenic response to cold exposure (50,51,74).…”