If increased non-shivering thermogenesis in mice plays a role in spaceflight-induced infiltration of bone marrow by fat and bone loss, there should be a strong post-landing association between restoration of normal thermoregulation and bone recovery. The rodent experiment design for the BION-M2 mission would provide an excellent platform for comprehensive analysis of relevant pathways regulating thermoregulation and bone metabolism and how these change during spaceflight and post-flight re-adaptation. To test our hypothesis we propose four Specific Aims.

Specific Aim 1. Hypothalamus: Determine the effects of spaceflight and re-adaptation on expression of genes related to sympathetic outflow.

Specific Aim 2. Brown adipose tissue (BAT): Determine the effects of spaceflight and re-adaptation on BAT histology and expression of genes related to non-shivering thermogenesis.

Specific Aim 3. White adipose tissue (WAT): Determine the effects of spaceflight and re-adaptation on WAT histology and expression of genes related to WAT turnover.

Specific Aim 4. Marrow adipose tissue (MAT): Determine the effects of spaceflight and re-adaptation on bone and MAT histology, lipid composition of bone marrow, and expression of genes related to bone cell and adipocyte turnover, and hematopoiesis. We will also characterize associations between changes in MAT, bone cells, and bone microarchitecture. We anticipate increased non-shivering thermogenesis in BAT as well as bone loss following spaceflight. Increased thermogenesis will be associated with increased sympathetic outflow from hypothalamus and WAT turnover. Bone loss will be associated with increased MAT, increased osteoclasts, and decreased hematopoiesis. During re-adaptation, we anticipate normalization of thermogenesis to occur prior to normalization of bone metabolism. Our analyses of histology, lipid composition of MAT, gene expression, and bone microarchitecture will provide insight into the specific pathways by which altered thermogenesis influences bone metabolism during spaceflight and during re-adaptation.

The proposed research is relevant to NASA because it will contribute to a mechanistic understanding of bone loss during spaceflight.

If increased non-shivering thermogenesis in mice plays a role in spaceflight-induced infiltration of bone marrow by fat and bone loss, there should be a strong post-landing association between restoration of normal thermoregulation and bone recovery. The rodent experiment design for the BION-M2 mission would provide an excellent platform for comprehensive analysis of relevant pathways regulating thermoregulation and bone metabolism and how these change during spaceflight and post-flight re-adaptation. To test our hypothesis we propose four Specific Aims.

Specific Aim 1. Hypothalamus: Determine the effects of spaceflight and re-adaptation on expression of genes related to sympathetic outflow.

Specific Aim 2. Brown adipose tissue (BAT): Determine the effects of spaceflight and re-adaptation on BAT histology and expression of genes related to non-shivering thermogenesis.

Specific Aim 3. White adipose tissue (WAT): Determine the effects of spaceflight and re-adaptation on WAT histology and expression of genes related to WAT turnover.

Specific Aim 4. Marrow adipose tissue (MAT): Determine the effects of spaceflight and re-adaptation on bone and MAT histology, lipid composition of bone marrow, and expression of genes related to bone cell and adipocyte turnover, and hematopoiesis. We will also characterize associations between changes in MAT, bone cells, and bone microarchitecture. We anticipate increased non-shivering thermogenesis in BAT as well as bone loss following spaceflight. Increased thermogenesis will be associated with increased sympathetic outflow from hypothalamus and WAT turnover. Bone loss will be associated with increased MAT, increased osteoclasts, and decreased hematopoiesis. During re-adaptation, we anticipate normalization of thermogenesis to occur prior to normalization of bone metabolism. Our analyses of histology, lipid composition of MAT, gene expression, and bone microarchitecture will provide insight into the specific pathways by which altered thermogenesis influences bone metabolism during spaceflight and during re-adaptation.

The proposed research is relevant to NASA because it will contribute to a mechanistic understanding of bone loss during spaceflight.

NOTE: Per F. Hernandez/ARC, there is no additional progress to submit for this reporting period. The NASA Space Biology Program has indicated that the project is presently on hold (Ed., 2/1/23).

If increased non-shivering thermogenesis in mice plays a role in spaceflight-induced infiltration of bone marrow by fat and bone loss, there should be a strong post-landing association between restoration of normal thermoregulation and bone recovery. The rodent experiment design for the BION-M2 mission would provide an excellent platform for comprehensive analysis of relevant pathways regulating thermoregulation and bone metabolism and how these change during spaceflight and post-flight re-adaptation. To test our hypothesis we propose four Specific Aims.

Specific Aim 1. Hypothalamus: Determine the effects of spaceflight and re-adaptation on expression of genes related to sympathetic outflow.

Specific Aim 2. Brown adipose tissue (BAT): Determine the effects of spaceflight and re-adaptation on BAT histology and expression of genes related to non-shivering thermogenesis.

Specific Aim 3. White adipose tissue (WAT): Determine the effects of spaceflight and re-adaptation on WAT histology and expression of genes related to WAT turnover.

Specific Aim 4. Marrow adipose tissue (MAT): Determine the effects of spaceflight and re-adaptation on bone and MAT histology, lipid composition of bone marrow, and expression of genes related to bone cell and adipocyte turnover, and hematopoiesis. We will also characterize associations between changes in MAT, bone cells, and bone microarchitecture. We anticipate increased non-shivering thermogenesis in BAT as well as bone loss following spaceflight. Increased thermogenesis will be associated with increased sympathetic outflow from hypothalamus and WAT turnover. Bone loss will be associated with increased MAT, increased osteoclasts, and decreased hematopoiesis. During re-adaptation, we anticipate normalization of thermogenesis to occur prior to normalization of bone metabolism. Our analyses of histology, lipid composition of MAT, gene expression, and bone microarchitecture will provide insight into the specific pathways by which altered thermogenesis influences bone metabolism during spaceflight and during re-adaptation.

The proposed research is relevant to NASA because it will contribute to a mechanistic understanding of bone loss during spaceflight.

January 2022 Report: To date there has been no progress because the spaceflight has not yet occurred and preparatory ground based studies have not yet been defined.

If increased non-shivering thermogenesis in mice plays a role in spaceflight-induced infiltration of bone marrow by fat and bone loss, there should be a strong post-landing association between restoration of normal thermoregulation and bone recovery. The rodent experiment design for the BION-M2 mission would provide an excellent platform for comprehensive analysis of relevant pathways regulating thermoregulation and bone metabolism and how these change during spaceflight and post-flight re-adaptation. To test our hypothesis we propose four Specific Aims.

Specific Aim 1. Hypothalamus: Determine the effects of spaceflight and re-adaptation on expression of genes related to sympathetic outflow.

Specific Aim 2. Brown adipose tissue (BAT): Determine the effects of spaceflight and re-adaptation on BAT histology and expression of genes related to non-shivering thermogenesis.

Specific Aim 3. White adipose tissue (WAT): Determine the effects of spaceflight and re-adaptation on WAT histology and expression of genes related to WAT turnover.

Specific Aim 4. Marrow adipose tissue (MAT): Determine the effects of spaceflight and re-adaptation on bone and MAT histology, lipid composition of bone marrow, and expression of genes related to bone cell and adipocyte turnover, and hematopoiesis. We will also characterize associations between changes in MAT, bone cells, and bone microarchitecture. We anticipate increased non-shivering thermogenesis in BAT as well as bone loss following spaceflight. Increased thermogenesis will be associated with increased sympathetic outflow from hypothalamus and WAT turnover. Bone loss will be associated with increased MAT, increased osteoclasts, and decreased hematopoiesis. During re-adaptation, we anticipate normalization of thermogenesis to occur prior to normalization of bone metabolism. Our analyses of histology, lipid composition of MAT, gene expression, and bone microarchitecture will provide insight into the specific pathways by which altered thermogenesis influences bone metabolism during spaceflight and during re-adaptation.

The proposed research is relevant to NASA because it will contribute to a mechanistic understanding of bone loss during spaceflight.

If increased non-shivering thermogenesis in mice plays a role in spaceflight-induced infiltration of bone marrow by fat and bone loss, there should be a strong post-landing association between restoration of normal thermoregulation and bone recovery. The rodent experiment design for the BION-M2 mission would provide an excellent platform for comprehensive analysis of relevant pathways regulating thermoregulation and bone metabolism and how these change during spaceflight and post-flight re-adaptation. To test our hypothesis we propose four Specific Aims.

Specific Aim 1. Hypothalamus: Determine the effects of spaceflight and re-adaptation on expression of genes related to sympathetic outflow.

Specific Aim 2. Brown adipose tissue (BAT): Determine the effects of spaceflight and re-adaptation on BAT histology and expression of genes related to non-shivering thermogenesis.

Specific Aim 3. White adipose tissue (WAT): Determine the effects of spaceflight and re-adaptation on WAT histology and expression of genes related to WAT turnover.

Specific Aim 4. Marrow adipose tissue (MAT): Determine the effects of spaceflight and re-adaptation on bone and MAT histology, lipid composition of bone marrow, and expression of genes related to bone cell and adipocyte turnover, and hematopoiesis. We will also characterize associations between changes in MAT, bone cells, and bone microarchitecture. We anticipate increased non-shivering thermogenesis in BAT as well as bone loss following spaceflight. Increased thermogenesis will be associated with increased sympathetic outflow from hypothalamus and WAT turnover. Bone loss will be associated with increased MAT, increased osteoclasts, and decreased hematopoiesis. During re-adaptation, we anticipate normalization of thermogenesis to occur prior to normalization of bone metabolism. Our analyses of histology, lipid composition of MAT, gene expression, and bone microarchitecture will provide insight into the specific pathways by which altered thermogenesis influences bone metabolism during spaceflight and during re-adaptation.

The proposed research is relevant to NASA because it will contribute to a mechanistic understanding of bone loss during spaceflight.